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THE PRINCIPLES 

OF 

Clinical Pathology 

A Text-Book for Students and Physicians 

BY 

DR. LUDOLF KREHL 

ORDINARY PROFESSOR AND DIRECTOR OF THE MEDICAL CLINIC IN STRASBURG 

AUTHORIZED TRANSLATION FROM THE THIRD GERMAN EDITION 

BY 

ALBION WALTER HEWLETT, M.D. 

INSTRUCTOR IN CLINICAL MEDICINE AT THE COOPER MEDICAL COLLEGE, 
SAN FRANCISCO, CAL. 

WITH AN INTRODUCTION BY 

WILLIAM OSLER, M.D. 

PROFESSOR OF MEDICINE AT THE JOHNS HOPKINS UNIVERSITY 




PHILADELPHIA AND LONDON 

J. B. LIPPINCOTT COMPANY 

1905 









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Copyright, 1904, by Ludolf Krehl 
Under the interim Copyright Act 

Copyright, 1905, by J. B. LlPPlNCOTT COMPANY 



Printed by J. B. Lippincott Company, Philadelphia, U. S. A. 



TRANSLATOR'S PREFACE 

¥¥ 

This volume is translated from the third German edition 
of Professor Krehl's " Pathologische Physiologic" I have, 
however, used the title of the first German edition, — viz., " The 
Principles of Clinical Pathology." This change was made 
partly because the terms pathological physiology are com- 
paratively unfamiliar to the English and American profession, 
and partly because it seemed desirable to emphasize the fact 
that the book deals especially with the problems that con- 
front the clinician. 

A literal translation was not attempted. Many abstract 
discussions have been abbreviated, and in a few places the 
material has been slightly rearranged, in order to present it 
in what seemed to be a more natural sequence. Yet no altera- 
tions of the author's views have been made, except these were 
indicated by enclosing them in parentheses ; and I have endeav- 
ored throughout to maintain the spirit of the original work. 
A few paragraphs have been added, mainly upon subjects that 
have attained a certain prominence in the recent American 
literature, such as the subjects of blood-pressure, surgical 
shock, and hemorrhagic pancreatitis. 

The original edition contains copious references to the 
German literature. Many of these have been omitted, more 
especially those referring to the older literature and to the 
well-known German text-books. In their place, I have added 
quite a number of English references, which may be of some 
assistance to those who do not read German and who desire to 
look up more elaborate discussions of many of the subjects. 

3 



4 TRANSLATOR'S PREFACE 

Unfortunately our own literature is often rather fragmentary ; 
for many of the fields dealt with have been developed almost 
exclusively by continental writers. 

In conclusion, I desire to express my indebtedness to Drs. 
W. E. Garrey, George Blumer, and W. F. Beerman for assist- 
ance in reading and correcting portions of the manuscript. 

A. W. HEWLETT. 
San Francisco. 



PREFACE TO THE THIRD EDITION 

In the present edition, a large part of which has been re- 
written, the attempt has been made to include the results of 
work published since 1897. Yet, in spite of the great pains 
taken, I dare not assert that all has been included and that 
even important researches have not been left out. I do not beg 
indulgence for such omissions, but can only state that I have 
never intentionally neglected to mention an important research, 
and that I have endeavored to make the book as complete as 
possible. Whoever has attempted to follow the literature in 
so many fields will recognize how difficult it is to master even 
fairly well the great diversity of material. 

L. Krehl. 
Tubingen, August, 1904. 



FROM THE PREFACE TO THE SECOND EDITION 

¥¥ 

The desire to write a book of this character arose from the 
conviction that two things are essential for a thorough knowl- 
edge of internal medicine. The first of these is skill in the art 
and technic of clinical medicine, which is only to be acquired 
by long and careful practice at the bedside. The second is the 
ability to judge disease in accordance with biological principles, 
for the study of disease is, ideally at least, an exact natural 
science. 

It is unnecessary to discuss the question as to which of the 
two is the more important. Both are necessary, and a deficient 
knowledge of either is detrimental to the clinician. If the latter 
be neglected, he becomes a mere routinist; whereas if insuffi- 
cient attention be paid to the former, he becomes an impractical 
theorist. 

The whole tendency of modern times precludes the possi- 
bility that the practical side of medicine should be neglected, 
for the extreme value of medical art and technic is now uni- 
versally recognized. Unfortunately, however, this recogni- 
tion has led to a certain antagonism toward theoretical and 
scientific work. Yet we must remember that, now as always, 
the solid foundation of all clinical knowledge rests upon the 
sciences of anatomy, physiology, and pathology; that, without 
these, technical skill in medicine would avail but little; and 
that the activities and views of the medical profession sink 

7 



8 PREFACE TO THE SECOND EDITION 

proportionately to their remoteness from the firm scientific 
foundations, and proportionately to the degree to which the 
clinician ceases to be a natural scientist. The purpose of this 
book, therefore, is to contribute to our knowledge of, and 
to awaken interest in, the theory of disease processes. 

L. Krehl. 
Leipzig, March, 1898. 



TABLE OF CONTENTS 

PAGE 

Introductory Note by Prof. Osler 13 

Introduction 15 

CHAPTER I. 

The Heart 21 

Importance of the Circulation, 21 ; Pulmonary Circulation, 21 ; 
General Circulation, 22 ; Adaptability of the Heart, 23 ; Hyper- 
trophy of the Heart, 28; Valvular Diseases, 30; Etiology of 
Valvular Disease, 30; Muscular Insufficiency, 33; Aortic Insuffi- 
ciency, 34; Aortic Stenosis, 38; Mitral Stenosis, 39; Mitral In- 
sufficiency, 40; Valvular Lesions of the Right Side, 41 ; Combined 
Valvular Lesions, 42 ; Hypertrophy of the Right Ventricle, 43 ; 
Hypertrophy of the Left Ventricle, 46; Hypertrophy of both 
Ventricles, 48; Cardiac Changes in Renal Disease, 49; The " Ath- 
lete's Heart," 53 ; The " Beer Heart," 54 ; Heart in Pregnancy, 
55 ; Ability of the Heart to Hypertrophy, 55 ; Concentric and 
Eccentric Hypertrophy, 56; Inefficiencies of a Compensated Cir- 
culation, 57; Myocardial Changes in Hypertrophied Hearts, 60; 
Causes of Broken Compensation in Hypertrophied Hearts, 63; 
Causes of Primary Insufficiency of the Heart Muscle, 65 ; Re- 
sults of Cardiac Weakness, 71 ; Disturbances of the Heart-Rate, 
77; Tachycardia, 78; Bradycardia, 83; Arrhythmia, 87; Forms 
of Arrhythmia, 88; Causes of Arrhythmia, 93; Cardiac Impulse, 
95; Heart Sounds, 96; Cardiac Murmurs, 100; Palpitation, 102; 
Cardiac Dyspncea, 103 ; Cardiac Pain, 105. 

CHAPTER II. 

The Blood-Vessels and the Lymph 108 

The Arterial Blood-Pressure, 109; Systolic and Diastolic Press- 
ures: Pulse-Pressure, 109; Physiological Variations in Blood- 
Pressure, in; Pathologically Increased Blood-Pressure, in; 
Pathological Diminution in Blood-Pressure, 112; Arterial Pulse, 
114; Venous Stasis, 115; Venous Murmurs, 115; (Edema, 116; 
Composition of Exudates, 121 ; Chylous and Chyliform Ascites, 
121 ; Pulmonary (Edema, 122. 



10 TABLE OF CONTENTS 

CHAPTER III. 

The Blood 125 

The Red Blood-Corpuscles, 126; Anaemia from Hemorrhage, 
126; General Considerations relative to Chronic Anaemias, 127; 
Chlorosis, 130; Secondary Anaemias, 133; Pernicious Anaemia, 
136 ; Haemoglobinaemia, 141 ; Haemolytic Action of Alien Plas- 
mas, 143 ; Paroxysmal Haemoglobinuria, 145 ; Other Causes 
which Injure the Red Blood-Corpuscles, 147; Systemic Effects 
from Rapid Destruction of Red Blood-Corpuscles, 148; The 
White Blood-Corpuscles, 149; Physiological Leucocytoses, 150; 
Pathological Leucocytoses, 152; Leucopenia, 154; Leukaemia and 
Pseudoleukaemia, 155 ; Plasma and Serum : Total Quantity of 
Blood, 162; Quantity of Fibrin, 162; Blood-Serum, 163; Cyto- 
lytic Properties of the Serum, 165 ; Antitoxins : The " Side- 
Chain" Theory, 167; Precipitins, 171; Agglutination, 172; Salts 
of the Serum, 174; Hydraemia, 174; Polycythaemia, 177; Ple- 
thora, 181. 

CHAPTER IV. 

Infection and Immunity 184 

Portals of Entry, 184; Natural Inherited Immunity, 189; Natural 
Acquired Immunity, 190; Active Artificial Immunity, 193; Pas- 
sive Artificial Immunity, 194; Phagocytosis and Immunity, 194; 
Conclusions, 195. 

CHAPTER V. 
The Respiration 197 

The External Respiration, 197 ; Means for Removing Harmful 
Material from the Air- Passages, 197 ; Stenosis of the Air- Pas- 
sages, 201 ; Bronchial Asthma, 206 ; Paralysis of the Respiratory 
Muscles, 208; Loss of Pulmonary Elasticity: Emphysema, 209; 
Changes in Respiration of Nervous Origin : Cheynes-Stokes Phe- 
nomenon, 211; Pleural Effusions and Pneumothorax, 213; Ate- 
lectasis, 215; Effects of Obliteration of Air-Spaces, 216; Effects 
of Atmospheric Pressure, 217; Inhalation of Poisonous Gases, 
220; Effects of Anaemia, 221; Respiratory Compensation, 223; 
Asphyxia, 225 ; The Internal Respiration, 226 ; Respiratory Sen- 
sations, 229. 

CHAPTER VI. 

The Digestion 231 

Mouth and GEsophagus, 231 ; Stomatitis, 231 ; Diminished Secre- 
tion of Saliva, 232 ; Ptyalism, 233 ; Composition and Reaction of 
Saliva, 234 ; Swallowing, 235 ; Oesophageal Stenosis, 236 ; Press- 
ure Diverticula, 237; Primary Dilatation of the (Esophagus, 238; 
The Stomach, 239 ; The Disturbances of Gastric Secretion, 241 ; 
Hypersecretion of Gastric Juice, 242; Round Ulcer, 244; Effects 



TABLE OF CONTENTS 11 

PAGE 

of Hypersecretion and Hyperacidity, 246; Subacidity and Anacid- 
ity, 247; Bacterial Action in the Stomach, 249; Disturbances of 
Motility, 252; Increased Peristalsis and Increased Motility, 254; 
Motor Insufficiency and Dilatation, 254; Causes of Dilatation, 
256 ; Effects of Motor Insufficiency, 258 ; Belching and Vomiting, 
260; Sensations from the Stomach, 262; Disturbances in the 
Secretion of Bile, 265 ; Gall-Stones, 266 ; Exclusion of Bile from 
Intestines, 271 ; Jaundice, 273 ; Other Hepatic Toxaemias, 277 ; 
Pancreatic Juice, 279 ; Fat Necroses, 281 ; Relation of the Bile to 
Pancreatic Disease, 282 ; Processes in the Intestines, 282; Effects 
of Poisons, 282 ; Abnormal Bacterial Processes within the Gastro- 
intestinal Tract, 284 ; Pathology of Absorption, 291 ; Disturb- 
ances in the Intestinal Movements, 293 ; Diarrhoeas, 295 ; Consti- 
pation, 298; Obstruction, 301; Strangulation, 307; Meteorism, 
308; Abnormal Intestinal Sensations, 310. 

CHAPTER VII. 

Nutrition and Metabolism 312 

Quantitative Variations in Metabolism of Fats and Proteids, 312; 
Caloric Needs of Body, 312; Proteid Needs of Body, 315; In- 
anition, 316; Effects of an Oversupply of Food, 319; Disturbances 
in Fat Metabolism, 322 ; Pathological Accumulations of Fat, 325 ; 
Pathological Destruction of Proteid Material, 330; Metabolism 
in Exophthalmic Goitre, 332; Qualitative Changes in Catabolism, 
335; Autolysis, 335; Formation and Excretion of Ammonia, 337; 
Production of Organic Acids, 339; Diabetic and Other Toxic 
Comas, 342 ; Relation between Hepatic Disease and the Excretion 
of Ammonia, 344; Alkaptonuria, 345. 

CHAPTER VIII. 

Disturbances in Carbohydrate Metabolism. Diabetes 347 

Alimentary Glycosuria, 348; Phloridzin Glycosuria, 349; Renal 
Diabetes, 351 ; Transient Glycosurias, 351 ; Diabetes Mellitus, 
352; Mild and Severe Forms, 352; Derivation of Sugar from 
Proteids and Fats, 353 ; Glycogenic Function of the Liver in 
Diabetes, 357 ; Consumption of Sugar in Diabetes, 358 ; Etiology 
of Diabetes, 361; Effects of Diabetes upon the Body, 362; 
Theory of Diabetes, 365. 

CHAPTER IX. 

The Metabolism of the Purin Bodies. Gout 368 

Gout, 370; Uric Acid in the Blood, 372; Uric Acid in the Urine, 
373 ; The Cause of the Local Deposits of Urates, 374 ; Theory 
of Gout, 375- 



12 TABLE OF CONTENTS 

CHAPTER X. PAGE 

Fever 376 

Normal Regulation of the Body Temperature, 377; Heat- Stroke, 
379; Heat Regulation in Fever, 381; Heat Production in Fever, 
382 ; Heat Losses in Fever, 384 ; Metabolism in Fever, 388 ; 
Cause of the High Temperature, 392; Site of Heat Production, 
393 ; Heat-Regulatory Mechanism in Fever, 395 ; Causes of 
Fever, 399; Variations in the Clinical Picture of Fever, 405; 
Nutrition in Fever, 406; Water Retention in Fever, 407; Sig- 
nificance of Fever, 408; Temperature in Collapse, 411 ; Subnormal 
Temperature, 412. 

CHAPTER XI. 

The Secretion of Urine 414 

Effects of an Increased Blood-Flow, 414; Diabetes Insipidus, 416; 
Effects of Diminished Blood-Flow, 417; Effects of Obstruction to 
the Escape of Urine, 418; Effects of Lesions of the Secreting 
Membrane, 419; Albuminuria, 420 ; Casts, 429; Effect of Changes 
in the Composition of the Blood, 429 ; Uraemia, 433 ; Urinary 
Passages, 436; Urinary Calculi, 438; Pain in the Urinary Pas- 
sages, 441. 

CHAPTER XII. 

The Nervous System 443 

Circulatory Disturbances, 443; Increased Cerebral Pressure, 446; 
Cerebral Concussion, 451; Disturbances of Motility, 452; Dis- 
turbances of Co-ordination, 456; Effect of Reflexes upon Motion, 
462; Nervous Disturbances of Urination and Defecation, 463; 
Alterations of Reflexes, 464 ; Strychnine Poisoning and Tetanus, 
467; Contractures, 468; Motor Irritative Symptoms, 471; Dis- 
turbances of Sensation, 473 ; Dizziness, 477 ; The Influence of 
the Nervous System upon Tissue Nutrition, 481 ; Muscular Atro- 
phies, 483 ; Herpes Zoster, 490. 



¥¥¥ 

LIST OF ILLUSTRATIONS 

¥¥ 

PAGE 

Fig. 1. — The effect of an extra stimulus applied to the ventricle ... 88 

Fig. 2. — The effect of an extra stimulus applied to the auricle .... 89 

Fig. 3. — Extrasystoles of the ventricular type 90 

Fig. 4. — Extrasystoles of the auricular type 91 

Fig. 5. — Tracing from a bigeminal pulse 92 



INTRODUCTORY NOTE 

Knowing its worth, I very gladly agreed to write a brief 
introductory preface to an American edition of Professor 
Krehl's well-known work. Not that it needs any words of 
commendation. A successful book in Germany, it has already 
been translated into several languages, and has long since 
passed beyond the probation stage; but a few words from me 
may serve to introduce it to the English-speaking profession. 
Those of us who were brought up on Williams's " Principles 
of Medicine" recall the pleasure and the profit derived from it, 
mingled now with the regret that we have no work of the same 
character to place in the hands of our senior students. This 
want Professor Krehl's book will supply. Herter's " Lectures 
on Chemical Pathology" cover part of the ground, and Cohn- 
heim's well-known " Lectures on General Pathology" is some- 
what similar. In Professor Krehl's work disease is studied as 
a perversion of physiological function, and the title " Clinical 
Pathology" expresses well the attempt which is made in it to 
fill the gap between empirical and scientific medicine. The 
facts presented are derived in part from studies upon patients, 
and in part from experiments upon animals, designed to ex- 
plain clinical problems. The author has had the advantage of 
prolonged laboratory training, to which has been added that 
accurate knowledge of disease to be had only by years of study 
and teaching in the wards. For such a work as this there is at 
the present time great need. Every few years the laboratories 
seem to run ahead of the clinics, and it takes time before the 
facts of the one are fully appreciated by the other. In the com- 
plexity of the problems, sometimes in the fascination of the sci- 
entific side, we are apt to lose sight of the practical application 

13 



14 INTRODUCTORY NOTE 

to diagnosis and to treatment of the facts obtained in the lab- 
oratories. The surgeons have invaded the medical wards with 
great advantage to our patients, and in many diseases to the 
great improvement in the art of diagnosis. How helpful it 
would be if clinicians had always at hand skilled physiologists, 
pathologists, and chemists to apply their most advanced tech- 
nique to clinical problems, and not the technique alone, but the 
biological and chemical principles upon which medicine as an 
exact natural science is founded. Principles, as Plato reminds 
us, require constant revision and consideration ; and this book, 
representing a revision to date of the " Principles of Clinical 
Pathology," will be most helpful to all students and teachers 
who wish to know the scientific basis of our art. 

William Osler. 



INTRODUCTION 

Pathological physiology is one among the sciences that 
contribute toward our knowledge of diseased processes. In his 
famous book on " General Pathology," Cohnheim has denned 
disease as a peculiar, abnormal course of the same processes 
that make up the life phenomena of healthy individuals. We 
term these vital processes normal when they occur in the ma- 
jority of individuals and when these latter feel well and are 
able to accomplish their average amount of work. 

In many instances, it is easy to determine whether the 
functions of the body are following a normal or an abnormal 
course ; in others, the question is a very difficult one to decide. 

The whole series of living 1 beings, from the lowest up to the 
highest, are liable to be afflicted with disease. Yet different 
species, even though they are closely related, may vary con- 
siderably from one another, not only in their morphological but 
in their functional characteristics. For example, it would be 
pathological if a mammal excreted as much uric acid in its 
urine as does a normal bird. The question as to whether a 
given function is or is not normal can only be answered by 
comparing individuals of the same species. 

These remarks might appear superfluous, inasmuch as the 
primary object of this book is to discuss pathological disturb- 
ances in man. Yet a satisfactory understanding of these latter 
is not possible except we make critical use of the data obtained 
from animals. 

I shall not attempt to discuss the outlook that the method 
of comparative study opens for us in our knowledge of patho- 
logical processes. Hitherto this method of study has played 
but a minor role in developing this field, for the means and 

'5 



16 INTRODUCTION 

opportunities for pursuing this line of work have been lacking. 
Yet if pathology is to remain abreast of the other branches of 
biology, we must have a closer relationship between the patho- 
logical and the veterinarian laboratories, and the natural dis- 
eases of animals must be studied with a view to the light that 
they may throw on those of man. Even now, extensive use is 
made of animal experiments in the study of pathological pro- 
cesses and these experiments have become an almost indispensa- 
ble aid in such study. In estimating the value of these experi- 
ments, however, due regard must be paid to the morphological 
and functional differences between man and the animals used. 

Very considerable individual differences may occur even 
within a single species. For example, there are men whose 
stomach contents at the height of digestion contain no free 
hydrochloric acid, and, although such men differ in this respect 
from the great majority of their fellows, nevertheless they may 
show absolutely no digestive symptoms and no diminution in 
their capacity for work. In my opinion, such individuals can 
hardly be regarded as being sick, although it must be acknowl- 
edged that they stand near the border line between the normal 
and the pathological. Another class of men show for years 
clear and unmistakable functional disturbances in some organ 
or group of organs, and yet they are not incapacitated to the 
slightest degree for work. Theoretically such men are sick; 
practically, we hardly know whether to say they are sick or 
healthy. 

The physician must be clear in his own mind about this 
great difference between the theoretical and the practical ; and 
although we are dealing in this book principally with the for- 
mer, yet it will not be amiss to emphasize this fact, that many 
individuals who show definite pathological changes are per- 
fectly healthy to all practical intents and purposes. 

We should designate as diseased, therefore, all those life 
processes which differ from the ones that occur in the majority 



INTRODUCTION 17 

of the members of a species, and which, in addition, affect 
the individual's capacity for work or the duration of his life. 

All theories of life processes, physiological as well as path- 
ological, must be carried back to the elementary constituents of 
the body. Disease arises from changes in a certain set of cells, 
or of organs, or of groups of organs ; for the cells that nor- 
mally work together are not necessarily grouped together, but 
they may be distributed over different parts of the body. We 
are learning more and more that certain functions necessitate 
the combined action of different classes of cells. 

Functional disturbances naturally coincide with, and are 
caused by, physical, chemical, or morphological changes in the 
body cells. This dictum is in no way altered by the fact that 
these chemical and morphological changes may not be demon- 
strable with the methods at our disposal. It is customary to dis- 
tinguish those disturbances in which no such changes in the 
cells have been found (functional disturbances) from those in 
which such changes have been demonstrated (organic lesions). 
Yet this distinction is a more or less accidental one, depending 
as it does upon what happens to be the state of our knowledge 
at the time when the division is made. 

A complete theory of pathological phenomena must embrace 
not only a knowledge of the functional disturbances in the 
affected cells, but a knowledge of their chemical, physical, and 
morphological changes as well. At present, our knowledge in 
all these directions is satisfactory for only a few diseases. For 
others, it has developed along functional and anatomical lines, 
for a third group, along functional and chemical lines, and 
finally, for a fourth group, the functional changes alone are 
known to us and we are ignorant as to their anatomical or 
chemical basis. 

The development of our knowledge in one or another of 
these directions depends in the first place upon the degree to 
which our methods of investigation can solve the problems pre- 

2 



18 INTRODUCTION 

sented. These methods will suffice for certain problems in cer- 
tain diseases but not for others, so that we have an unequal de- 
velopment along different lines. In the second place, the master 
minds of the time tend to develop our knowledge along the lines 
that happen to interest them most, and these lines gain thereby 
a certain prominence. Controversies have been waged and still 
are waged as to which is of greatest importance, the functional, 
chemical, or morphological view of disease. The uselessness of 
such a controversy is apparent when we remember that all these 
changes necessarily go together and that we must look at a dis- 
ease from every point of view. Nevertheless, it is true that one 
point of view may be more luminous than another in respect to 
any particular class of diseases. 

Diseases result either from primary defects in the living 
protoplasm or from the protoplasm being placed under such ab- 
normal conditions that it cannot compensate for the changes in 
its environment. In the first class of cases, the abnormality 
consists in an improper organization of the protoplasm. The 
affected individual is then either diseased from birth, or he is 
born apparently healthy but is unable to withstand the ordinary 
wear and tear of life as a normal person should. Consequently, 
the structure, composition, or functions of his tissues suffer. 
Such primary endogenous weakness apparently plays a not in- 
considerable role in the etiology of disease. 

Of greater importance, however, is the effect that injurious 
external influences exert upon the living substance of the body. 
When these injuries affect the composition, structure, or func- 
tions of the cells, they become causes of disease. These causes 
are of the most varied kinds. Heat and cold, humidity and dry- 
ness, electricity, chemicals, all these may affect the body; but 
more important than any of them is the penetration of abnor- 
mal forms of life into the body. 

Whether a man shall become sick or not, depends, therefore, 
in the first place, upon the way that he is originally constituted 



INTRODUCTION 19 

(endogenous causes), and, in the second place, upon the more 
or less accidental injuries to which he is exposed (exogenous 
causes). Furthermore, the effectiveness of the latter class of 
causes depends largely upon factors that lie within the indi- 
vidual. There are, indeed, poisons, which, in a certain dose, will 
kill practically any one, and there are infections that will attack 
all or nearly all individuals exposed to them. Nevertheless, the 
majority of all infectious and toxic processes affect only a cer- 
tain proportion of the individuals exposed. The causes of this 
difference in susceptibility are naturally complex and not 
always the same ; but in the main they depend upon the physio- 
logical organization of the individual. 

In a complete discussion of diseased phenomena, the vital 
processes and the alterations in these processes and in the ele- 
mentary constituents of the body must be considered from 
various points of view. In the present book, we propose to 
present only one of these. Just as physiology deals with the 
functions of the normal body, so pathological physiology deals 
with the functions when organs are placed under pathological 
conditions; and this is the subject of our discourse. 

The field covered by this book serves, in the main, to fill out 
the gap left in the subject of pathology after the subjects of 
general pathology and of special pathological anatomy have 
been eliminated. In classifying the material, I have followed 
the classification that is customary in the German universities, 
and I have utilized material that has especially appealed to me 
as a clinician. Many subjects that are usually discussed in our 
text-books on general pathology, such as local circulatory dis- 
turbances, have been omitted, even though they should rightly 
be included in a book of this character. Whether the choice of 
material has been a fortunate one or not, remains to be decided. 



THE PRINCIPLES 



CLINICAL PATHOLOGY 



CHAPTER I. . 

THE HEART. 

The Importance of the Circulation. — The circulation is of 
fundamental importance to the body. It is not, of course, true, 
as was formerly believed, that the functions of the individual 
organs depend primarily upon the amount of material that 
they receive from the blood. Without doubt their activities 
depend rather upon the condition of the parenchyma cells and 
upon the stimuli which these receive from the nervous system. 1 
Yet it is certain that, in warm-blooded animals at least, a 
sufficient supply of oxygen, salts, and food materials to the 
tissues is a necessary requisite for a normal course of life. Dis- 
turbances of the circulation are therefore of great importance, 
and the more complex the organ affected, the more serious are 
the results of such disturbances. 

The Pulmonary Circulation. — A disordered condition of 
the circulatory system may have its origin either in the pump 
which propels the blood or in the tubes through which the blood 
flows. The right ventricle drives venous blood at a compara- 
tively low pressure through the pulmonary vessels, which form 

1 We are, however, now acquainted with at least one example demon- 
strating that the blood may normally carry a specific substance which 
Stimulates an organ to activity, — viz.. the secretin, stimulating the pan- 
creas. — Ed. 

21 



22 CLINICAL PATHOLOGY 

a system of short tubes, whose combined area of cross-section 
is very great. Through the walls of these capillaries, the 
interchange of gases between the blood and the air in the lungs 
occurs; and since this interchange takes place quite rapidly, 
the pulmonary system of a large number of short tubes seems 
best fitted for the work to be performed. The vessels play a 
relatively subordinate part in controlling the circulation in 
the lungs, for the pulmonary arteries possess little, if any, 
tone. 2 So far as we know, the different parts of the lungs 
are functionally equal, and there seems to be no necessity for 
a variation in the blood-supply to different pulmonary areas. 
During a period of rest, when only a slight interchange of 
gases is necessary, the rate of blood-flow in the lungs is com- 
paratively slow; but during exercise, when larger amounts 
of gases must be interchanged, a great quantity of blood is 
propelled through the lungs. The increased respiratory move- 
ments assist the action of the heart in maintaining this more 
rapid circulation. 

The General Circulation. — The relations are quite different 
in the greater circulation. Here a higher blood-pressure pre- 
vails at the onset, its height depending upon the contractions 
of the left ventricle, and upon the size of the smaller arteries. 
Variable amounts of blood may be made to pass through dif- 
ferent organs without any alteration of the general arterial 
pressure, for, as the resistance to the flow of blood through one 
organ is lessened, the resistance to the flow through another 
may be correspondingly increased. Such a mechanism is of the 
greatest service, for here all parts are not of equal functional 
value, as they are in the case of the lungs, and it may be neces- 
sary to furnish one organ with a rich supply of blood at one 
time, and then later to do the same for another. The activity 
of the muscle-fibres of the smaller arteries regulate the distribu- 
tion of the blood without at the same time necessarily altering 

' Knoll, Wiener Sitzungsber. mathem. naturw. Kl., 1899, iii. p. 5. 



THE HEART 23 

the general blood-pressure. Indeed, this latter must not sink 
below a certain point if the brain and eye are to perform their 
functions properly. 

The flow of blood in the veins is caused in part by the slight 
blood-pressure transmitted through the capillaries from the 
arteries and in part by other accessory forces. Of these, we 
may mention the suction exerted by the heart and the thoracic 
cavity, as well as the pumping effect produced by the varying 
pressure of the muscles and fasciae upon those veins that are 
provided with valves. 

The Adaptability of the Heart. — Any of the various parts 
of the cardiovascular apparatus may be diseased without neces- 
sarily disturbing the general circulation. This is due to the 
fact that this apparatus, like so many others in the animal body, 
possesses a compensatory mechanism. We need not regard 
this mechanism as the provision of a beneficent Providence, 
arming man against disease, nor need we regard it as a trait 
acquired in the struggles of the race against injurious agents. 
The compensatory mechanism for pathological processes is 
simply that which a healthy man possesses and uses in order to 
meet the varying physiological demands made upon the circu- 
lation. 

The amount of work which the heart performs 3 may be 
approximately estimated if we know the volume of blood de- 
livered at each systole, the velocity imparted to this blood, the 
peripheral resistance, and the number of heart-beats in a unit 
of time. In other words, it depends upon the size of the ven- 
tricular cavity in diastole, the number and intensity of the 
ventricular contractions, and the degree of constriction of the 
blood-vessels. The latter, in the lesser circulation, depends 
primarily upon the condition of the lungs, whereas in the 
greater circulation it depends upon the condition of the smooth 

'R. Lewy, Ztft. f. klin. Med., vol. xxxi. pp. 321, 520; O. Frank, Ztft 
f. Biol., vol. xxxii. p. 428, and vol. xxxvii. p. 483. 



24 CLINICAL PATHOLOGY 

muscle-fibres of the arteries and upon the vasomotor nerves 
which supply them. 

During the life of a healthy individual, the blood flows at 
varying rates of speed, — rapidly when the cells need much 
oxygen or food material, slowly when this need is small. As 
stated above, it is possible that the blood-supply to an organ, 
or possibly to several organs, should vary greatly without 
affecting the general blood-flow. This is brought about by a 
contraction in one set of vessels, which contraction compen- 
sates for a dilatation in another set. Yet this compensation 
cannot meet all emergencies on account of the limited quan- 
tity of blood in the body. When large amounts of blood are 
needed in several parts of the body at the same time, they 
can only be furnished by increasing the speed of the general 
blood-stream. 

We might think that propelling a larger amount of blood 
would not necessarily increase the work of the heart, for, as the 
volume of blood increased, the general blood-pressure might 
be so decreased that the two would counterbalance each other. 
As a matter of fact, however, this does not occur, and, indeed, 
could not occur, on account of the relations that exist between 
the amount of blood propelled, the general pressure, and the 
rate of flow. For example, if an extra supply of blood to the 
body were necessary, a diminution in the general arterial press- 
ure would so reduce the difference in pressure between the ar- 
teries and the veins that the rate of flow in the capillaries 
would be insufficient to keep the heart supplied with fresh 
blood. Thus any great increase in the rate of flow is incom- 
patible with a lessened arterial pressure, and consequently such 
an increased flow necessarily entails more work for the heart. 

The work of the heart may be increased in another way, — 
viz., by increasing the peripheral resistance. The latter varies 
frequently and considerably even in health, for we know that 
the irritation of numerous sensory nerves will call forth con- 



THE HEART 25 

tractions of the smaller arteries and therewith increased re- 
sistance. It is theoretically possible that this increased resist- 
ance should be overcome without additional work for the heart, 
provided that as the resistance is increased, the amount of blood 
delivered is correspondingly decreased. Such a condition, 
however, would slow the circulation so that the body could 
not perform its functions properly, and, as a matter of fact, 
it does not occur. We may therefore say that any marked 
increase in the peripheral resistance necessitates more work 
for the heart. 

The heart is the best motor known to man. It performs 
equally well the small amount of work necessary when a man is 
at complete rest, and the large amount necessitated by great 
exertion. It therefore possesses the power of adapting itself to 
the varying demands made upon it. Not every man's heart is 
capable of the most extreme exertion, and a tailor in a large 
city could hardly furnish the circulation necessary for the 
ascent of the Matterhorn. The weight of the muscular tissue 
of the heart, and with this its capabilities, bears a certain rela- 
tion to the weight of the skeletal muscles. The tailor is unable 
to ascend the mountain mainly because his general musculature 
is weak. If this be improved by training, then the heart also 
increases in its capabilities, and usually at a more rapid rate. 
Indeed, a healthy heart rarely fails in any effort. It pos- 
sesses extreme adaptability, and what is of greater impor- 
tance, the adaptation occurs precisely at the time when it is 
most needed. To this fact the body owes its remarkable 
capacity for work. For example, when a ventricle in diastole 
becomes unusually filled (even up to six times its customary 
capacity), 4 then with the next systole, it drives out not all the 
blood, perhaps, but at least several times the ordinary quantity. 
On the other hand, if the arterial resistance be suddenly in- 
creased, it is as promptly overcome by the succeeding ven- 

4 Stolnikow, Du Bois' Arch., 1886, p. 1. 



26 CLINICAL PATHOLOGY 

tricular contractions. There is no time lost in experimentation. 
The demand and the accomplishment occur together. 5 This 
wonderful adaptability of our heart expresses itself both in its 
powers of dilatation and of contraction. Thus in diastole the 
ventricles will readily expand and take up greater amounts of 
blood without a corresponding increase in their tension. Only 
a slight pressure is necessary to distend the heart after the first 
short period of suction is passed. 6 When the ventricle is nearly 
filled, however, the tension rapidly increases. The same occurs 
even though much larger amounts of blood must flow into the 
heart during each diastole. The elasticity of the heart muscle, 
which governs the resistance to the inflowing blood, must there- 
fore vary with the amount of fluid that is to enter the heart. 
By means of this variation it is possible for the ventricle to 
receive very different amounts of blood within the same period 
of time. 

The contractility of the heart also bears a certain relation 
to the amount of blood to be propelled. It also accommodates 
itself to the increased demand. The ventricle is therefore able 
to expel, almost completely, much more blood than usual, and 
to do this even against greatly increased resistance. 

Without doubt this remarkable adaptability is a function of 
the muscle itself. 7 For the heart muscle, presumably free of 
all ganglion cells and nervous connections, possesses the above 
properties to precisely the same degree as does the intact 
organ. 8 The actual cause of the accommodation is not under- 
stood. So far as we know, the heart uses all its muscle-fibres 
at each contraction. The increased work, therefore, is accom- 

6 Cohnheim, Allg. Path. ; v. Frey and Krehl, Du Bois' Arch., 1890, 
p. 31; v. Frey, Arch. f. klin. Med., vol. xlvi. p. 398; O. Frank, Ztft. k. 
Biol., vol. xxxii. p. 370. 

9 Hesse, Arch. f. Anat, 1880, p. 328. 

7 Ludwig and Thiry, Wien. Sitzungsber., vol. xlix. II. p. 421. 

8 v. Frey, Arch. f. klin. Med., vol. xlvi. p. 398; Krehl and Romberg, 
Arch. f. exp. Path., vol. xxx. p. 49. 



THE HEART 27 

plished, not by calling new fibres into play, but by causing the 
old to contract more quickly and more energetically. How is 
this brought about? In a skeletal muscle, poisoned by curare, 
the strength of the contraction depends not only upon the stim- 
ulus, but upon the weight to be lifted. If we ascribe similar 
properties to the heart muscle, we are led to the conclusion 
that the amount of distention directly regulates the force of 
the subsequent contraction, v. Frey rightly remarks that the 
response occurs too quickly to be a reflex act. " It frequently 
happens that the heart does not feel the increased resistance 
until the beginning of systole. It is then already too late for 
a reflex adjustment, and, if it waited for that, the next con- 
traction would be abortive. Experience, however, shows that 
this is not the case. The contractions which follow imme- 
diately after an increased call upon the heart are, as a rule, 
unusually powerful." 

Although the nervous system is not necessary for this adap- 
tation, yet it would seem that, in many cases, both the elasticity 
and the contractility may be increased by nervous influences. 
Kauders 9 has performed a remarkable series of experiments, in 
which he has shown that an increased resistance, produced by 
an irritation of a sensory nerve (e.g., the sciatic), is better 
overcome by the left ventricle than the same degree of resist- 
ance produced by direct compression of the aorta. In the latter 
case the left ventricle failed to do its work, and the pressure 
in the left auricle increased; whereas in the former the work 
was not only well done, but the auricular pressure was even 
diminished. The left ventricle worked here to better purpose, 
probably because it was favored by nervous influences from the 
medulla. 

As has been shown above, when the peripheral resistance 
is increasd or when there is a demand for a greater blood- 

• Ztft. f. klin. Med., vol. xxi. p. 61 ; Grossman, ibid., vol. xxvii. p. 
I5i- 



28 CLINICAL PATHOLOGY 

supply, the heart can only meet the new requirements by 
doing more work. The slightly lengthened systole, which may 
occur under these circumstances, and which amounts to not 
more than from twenty to thirty per cent., does not lessen the 
work sufficiently to compensate for the other factors. 

The heart's capacity for work is certainly very great. Even 
though, experimentally, the amount of blood in the ventricles 
during diastole be increased sixfold, they are able to empty 
themselves almost completely, and a doubling of the arterial 
pressure does not cause serious embarrassment. Yet, on the 
other hand, an increase in the heart's activities is not without 
its disadvantages. For, in the first place, the increased work 
is only possible by increasing the chemical decomposition in its 
muscle, and, in the second, an excessive rise in arterial pressure 
is by no means without danger, especially if the blood-vessels 
are not perfectly healthy. 

Hypertrophy of the Heart. — Frequent and marked increase 
in the work of the heart leads to secondary changes. In this 
respect, so far as we know, the heart acts precisely like a 
striated muscle. Continued exertion leads to its enlargement, 
owing to the increase in size and number of its muscle-fibres. 
It then reaches a new equilibrium, and is able to accomplish 
without effort tasks that formerly called its reserve force 
into play. Bauer 10 designates this as a " strengthening of 
the heart." When an increased effort is demanded of it, the 
work is divided among more numerous and stronger fibres, 
and it is therefore more easily performed. The extreme limits 
of accommodation have also become greater, for we may 
assume that the stronger hypertrophied muscle possesses a 
greater reserve force than the former weak muscle, and ex- 
perience seems to bear out this assumption. 

If the weight of the heart muscle depends upon the amount 
of work done, then we should expect that the weight would 
10 Festschr. f. Pettenkofer, Munich, 1893. 



THE HEART 29 

vary in different individuals. 11 In the numerous and careful 
observations of W. Miiller, 12 and of Hirsch, 13 such a varia- 
tion has been demonstrated, there being a definite relation be- 
tween the weight of the heart and the total weight of living 
body tissue. We have no method of directly determining the 
amount of work that has been performed by a heart. Perhaps 
it would be of value to know the work done by the body as a 
whole, although different sorts of work affect the circulation 
differently. It is also difficult to determine the total weight of 
living tissue in a body or even that of the muscular system, 
which is of special importance. Thus far, statistics have dealt 
with the relation that exists between the weight of the heart 
and the total body weight, and although the latter introduces 
inaccuracies on account of the varying amount of fat and the 
presence of oedema, nevertheless the figures from a large 
amount of material have shown that the ratio between the 
weight of the heart and that of the body varies only within 
narrow limits ; from which consideration, Hirsch concludes 
that the activity and weight of the body musculature exercise 
a determining influence upon the weight of the heart. 

If this ratio of the weight of the heart to the body weight 
be increased, we speak of an hypertrophy of the heart. Al- 
though such an hypertrophy may arise from a variety of causes, 
it is questionable whether it ever results from prolonged ex- 
ertion alone. We know that severe muscular exertion in- 
creases the weight of the heart, for the amount of blood to be 
propelled is much greater than normal and the arterial pressure 
is not diminished, but is usually increased. 14 Under these 
circumstances, the heart necessarily becomes larger, but this 
increase in size is not usually out of proportion to the accom- 

" See Krehl in the Nothnagel System. 

12 Die Massenverhiiltnisse des menschlichen Herzcns, Hamburg, 1884. 

" Arch. f. klin. Med., vol. lxiv. p. 597. 

"Moritz, Arch. f. klin. Med., vol. lxxvii. p. 339. 



30 CLINICAL PATHOLOGY 

panying increase in the skeletal musculature. We possess no 
very exact anatomical observations on the size of the heart 
under such conditions. Clinical examination, however, usually 
fails to show any hypertrophy. Yet two observations speak 
in favor of the view that hypertrophy without weakness may 
result from prolonged overexertion. Race-horses possess rela- 
tively large hearts, 15 and skid-runners of Denmark who were 
apparently healthy have been shown in several instances to 
have hypertrophy of the left ventricle. 16 We may, therefore, 
say that a relative increase in the weight of the heart as a re- 
sult of overexertion is a great rarity, and that, when it occurs, 
it is usually due to pathological changes in the muscle. We 
shall return to this subject in speaking of heart hypertrophy. 

Valvular Disease of the Heart. — As has been said, the 
heart possesses the power of adjusting itself to varying cir- 
culatory conditions, which would otherwise interfere seri- 
ously with the supply of blood to the body. It exercises this 
power not only to meet the varying demands made upon it 
during health, but to compensate for the destructive processes 
wrought by disease. 

The function of the valves of the heart is to direct the 
current of blood in the proper direction. In order to prevent 
leaks, the valves must be intact, they must be properly con- 
trolled by the papillary muscles and the chordse tendineae, and 
the openings which they close must be reduced in size by the 
contraction of the surrounding ring of muscle, a most impor- 
tant factor. The orifices of the heart become much smaller 
during systole, at which time they may be readily closed, 
whereas during diastole they are relatively too large for the 
valves. 

The Etiology of Valvular Disease. — Diseases of the valve 

15 Friedberger and Frohner, Spez. Path. u. Ther. der Hausthiere, 1896, 
vol. i. p. 503. 

"Henschen, Mitteil, aus der med. Klin, zu Upsala, Jena, 1899, p. 53. 



THE HEART 31 

segments may be produced by micro-organisms or their toxins. 
Acute articular rheumatism and the septic diseases are the most 
frequent causes of valvular heart lesions. Next to these we 
may name typhoid fever, scarlet fever, variola, chorea, and 
gonorrhoea. Indeed any infectious disease may injure the 
heart valves. 17 

The bacteria most frequently found in acute endocarditis 
are the streptococci, staphylococci, and pneumococci, although 
other organisms, as gonococci, are occasionally present. 18 In 
a number of instances, as in gonorrhceal endocarditis, the heart 
is simply one localizing point of a general infection. In other 
cases, as in the acute exanthemata, the heart complications are 
to be regarded as the result of secondary infections. The origi- 
nal disease prepares the ground for the invasion of the organ- 
isms which attack the heart valves. 

Not infrequently no bacteria are found in the endocardial 
vegetations. It is possible in such instances that organisms 
have been present, but that they have died out. On the other 
hand, such an endocarditis may possibly be produced, not by 
the local action of micro-organisms, but by toxins generated in 
some other part of the body. No micro-organisms are found, 
as a rule, in the endocarditides complicating carcinoma, tuber- 
culosis, or nephritis. Not infrequently none have been found 
in the rheumatic endocarditis, but from other cases of this dis- 
ease various bacteria have been isolated. The real cause of the 
heart complications of rheumatism is of considerable interest, 
for rheumatism is analogous in many ways to an infection with 
the pyogenic cocci. 

Infections may attack different parts of the heart; certain 
ones showing a tendency to localize on the valves, others v to 
involve more especially the myocardium. The injury to the 

17 Worobjcvv, Arch. f. klin. Med., vol. xlix. p. 466. 
"Lenharz, Deut. med. Wochenschr., 1901, Nos. 29 and 30; M. Loeb, 
Arch. f. klin. Med., vol. Ixv. p. 411. 



32 CLINICAL PATHOLOGY 

valves begins with a degeneration of the endothelium, quickly 
followed by a deposit of blood-platelets and of thrombi. The 
tissue reaction comes later, and is more marked when the auric- 
ulo-ventricular valves are affected than when the semilunar 
valves are diseased. 

It is not our purpose to discuss the different anatomical 
and clinical forms of endocarditis. It suffices to recall that by 
ulceration and shrinkage the valves may be shortened or per- 
forated, and that by adhesions along their margins the orifices 
may be narrowed. Furthermore, owing to a concomitant myo- 
cardial affection, the orifices may not be properly constricted 
during systole, or the auriculo-ventricular valves may not be 
properly controlled by the chordse tendinese. These latter fac- 
tors are of no little importance. For example, when at autopsy 
we see only a slight marginal affection of the mitral valve, 
whereas during life there had been a decided functional insuffi- 
ciency, we must regard the complicating myocarditis rather 
than the valve lesion as the cause of the disturbances in func- 
tion. 19 No one who understands the closure of the auriculo- 
ventricular orifices can believe that such a minimal affection of 
the valve could possibly be the sole cause of a serious insuffi- 
ciency. It is an interesting fact that the endocarditides, com- 
plicating ulcerating carcinomata and tuberculosis, are much 
less frequently diagnosticated than are those complicating 
rheumatism. Since the myocarditis is usually absent in these 
cases, the muscular rings contract well during systole, and the 
heart is less likely to be rendered insufficient from the valvular 
affection. 

Chronic endarteritis is another important etiological factor ' 
in the production of valvular disease. This usually spreads 
from the aorta to the valves, but it may originate primarily in 
the latter. 

Finally, the insufficiency may develop because the valves or 

19 Romberg, Arch. f.. klin. Med., vol. liii. p. 141. 



THE HEART 33 

chordae tendinese are torn during very severe exertion, as a 
result of the great rise in intracardiac pressure, a very un- 
common accident. 20 

The large thrombi which are sometimes found in the left 
auricle may hinder the flow of blood, and even produce the 
symptoms of a mitral stenosis. The clinical signs and symp- 
toms so produced are not as yet well understood. 

The effects of valvular lesions may show themselves in two 
different ways, — either the orifices are not properly closed when 
they should be (insufficiency), or they cannot open widely 
enough to allow the blood to pass through freely (stenosis). 
Whether, in a given case, the one or the other occurs, or, as 
frequently happens, both occur together, depends upon the na- 
ture of the anatomical changes present. 

The seat of the disease is in part dependent upon the causa- 
tive factor. The arteriosclerotic lesions most frequently affect 
the left semilunar valves on account of their proximity to the 
aorta. As a rule, a fresh endocarditis will produce an insuffi- 
ciency and not a stenosis. The valvular vegetations in con- 
junction with the diseased heart muscle render the closure of 
the valves imperfect; whereas in order to produce a stenosis, 
a chronic inflammation with ultimate adhesions between the 
valve leaflets is necessary. The grade of insufficiency, or of 
stenosis, — i.e., the amount of blood which in the former case 
flows back, and in the latter is hindered from passing through 
the orifice, — is determined partly by the condition of the heart 
muscle and partly by the anatomical changes in the valves. 

Muscular Insufficiency. — We have already mentioned the 
great importance of a proper constriction of the valvular ori- 
fices during systole by the surrounding ring of muscular tissue. 
A faulty constriction may entail serious consequences, and the 
so-called muscular insufficiencies are much more common than 
is generally supposed. They occur most frequently as a result 

30 M. B. Schmidt, Munch, med. Woch., 1002, No. 38. 
3 



34 CLINICAL PATHOLOGY 

of myocardial disease, and in chronic myocarditis, especially, 
they may lead to precisely the same disturbances of function as 
does a shortening of the valve segments. Indeed, the diag- 
nosis between the two is often extraordinarily difficult, and 
many reported instances of " healed valvular disease" are 
doubtless merely improved cases of myocarditis with muscu- 
lar insufficiency. 

Muscular insufficiencies occur much more frequently at the 
auriculo-ventricular orifices than at the semilunar openings. 
At the mitral orifice they are usually due to a faulty contraction 
"of the surrounding ring of muscle, or possibly at times to a lack 
of control of the valve segments by the papillary muscles and 
chordae tendineae. On the right side of the heart the contrac- 
tion of the ventricle, as a whole, is usually at fault. According 
to v. Jurgenson, the slow contraction of the fatigued muscle 
may also interfere with the closure of the valves. 21 The term 
" relative insufficiency" has been used for the condition in 
which the orifice is so widened that the valves are no longer 
able to close it. Although this " stretching" of the opening 
may, indeed, occur, we must insist that, after all, the essential 
factor is not the dilatation of the ring, but the faulty constric- 
tion during systole. 

A relative insufficiency of the valves at the entrance to the 
aorta is much less uncommon. 22 At times it is due to an 
insufficient development of the muscle just beneath the semi- 
lunar valves, or it may originate in a dilatation of the fibrous 
ring at the beginning of the aorta. 

Aortic Insufficiency. — It is now necessary to point out how 
the various valvular lesions affect the distribution of the blood 
in the body, and how the heart accommodates itself to the new 
conditions arising from the valvular defects. 23 

21 v. Jurgenson, in Nothnagel's System. 

22 Popow, Petersb. med. Wochenschr., 1902, No. 45. 

23 Moritz, Arch. f. klin. Med., vol. lxvi. p. 349 ; D. Gerhardt, Arch. f. 
exp. Path., vol. xlv. p. 186. 



THE HEART 35 

When there is an insufficiency of the aortic valves, a part of 
the blood that is thrown into the aorta by the contraction of 
the left ventricle returns again into that cavity during diastole. 
The amount that flows back is determined by the size of the 
pathological opening left by the improper closure of the valves, 
by the difference between the pressure in the aorta and that in 
the ventricle, and by the duration of diastole. An increased 
heart-rate, which shortens more especially the diastolic period, 
should be of advantage in aortic insufficiency since it lessens 
the amount of the leak backward. Clinically, a rapid heart 
action is not infrequently found associated with this lesion, 24 ' 
but we are ignorant of its cause. The walls of the ventricle are 
very flabby during diastole, so that they are easily stretched by 
the stream of blood flowing in under high pressure from the 
aorta. This leads to a dilatation of the ventricular cavity, and 
the amount of dilatation depends upon the quantity of blood 
which flows back and upon the degree of elasticity of the 
muscle wall. In early diastole the ventricular wall is par- 
ticularly flabby, as the filling proceeds it becomes more tense, 
and toward the end of diastole the tension increases rapidly. 
By thus increasing the resistance to the inflowing blood the 
ventricle can protect itself against overdistention. We have 
already seen that this resistance varies normally according to 
the varying amounts of blood which must be delivered, and that 
the ventricular wall becomes more distensible whenever larger 
quantities of blood must be propelled (p. 267). The abnormal 
filling of the ventricle in aortic insufficiency may or may not 
act as a hinderance to the entrance of blood from the auricle. 
Whether the one or the other occurs depends mainly upon 
this variation in the elasticity of the ventricular musculature. 
If this change, so as to accommodate the extra amount of blood, 
then it is possible that the auricle will empty itself as usual and 
that there will be no disturbance in the flow of blood from the 
** Levy, Ztft. f. klin. Med., xxxi. p. 539. 



36 CLINICAL PATHOLOGY 

lungs. Such cases do occur, and have been observed both clin- 
ically and experimentally. 25 

On the other hand, many patients with aortic insufficiency- 
show symptoms referable to a damming back of blood into 
the lungs. Their dyspnoea and the marked accentuation of the 
second pulmonic sound are indicative of increased pressure in 
the pulmonary circulation. It is easy to understand how this 
might be brought about by an uncomplicated aortic regurgita- 
tion. It is only necessary for the tension of the ventricular 
wall to increase before all the blood from the lungs had entered 
the ventricle. This would hinder the entrance of blood from 
the auricle and would tend to produce a pulmonary congestion. 
Furthermore, the suction of blood from the lungs due to the 
expansion of the ventricle in early diastole may also be dimin- 
ished owing to the stream entering from the aorta. We have 
both clinical and experimental evidence that under such cir- 
cumstances a pure aortic regurgitation may cause a stasis of 
blood in the lungs. 26 

In spite of its increased contents, the left ventricle in aortic 
regurgitation empties itself in about the same length of time 
as does the normal ventricle, although according to recent 
observations 27 it may not empty itself so completely. For 
there is evidence that the blood is not usually entirely expelled 
during systole if the ventricular cavity be greatly dilated. This 
fact, however, is really of no great importance in the matter 
under consideration, for so long as the ventricular muscle is 
efficient, the residue of blood left in the cavity at the end of 
systole is insignificant compared with that which streams back 
from the aorta during diastole. 

In a series of classical experiments, Rosenbach 28 has shown 

25 Kornfeld, Ztft. f. klin. Med., vol. xxix. pp. 91, 344, 450. 
28 Kornfeld, loc. cit. ; Romberg and Hasenfeld, Arch. f. exp. Path., vol. 
xxxix. p. 333. 

27 Johanssen and Tigerstedt, Skan. Arch. f. Phys., vol. i. p. 331. 
23 Arch. f. exp. Path., vol. ix. p. 1. 



THE HEART 37 

that after artificially puncturing the aortic valves of a dog, all 
the symptoms of an insufficiency occur without any marked 
lowering of the mean arterial pressure. Since then this experi- 
ment has been frequently repeated, but with varying results. 
In rabbits the mean pressure is usually lowered as a result of 
the operation, whereas in dogs it may remain normal, be 
lowered, or even be raised. These variable results probably 
depend, in the first place, upon the strength of the heart, and, 
in the second place, upon the severity of the lesion. The rab- 
bit's weak heart cannot so readily compensate for the injury, 
and its blood-pressure sinks. The dog's stronger heart readily 
overcomes a slight injury (e.g., puncture of the valve by a 
rod) ; whereas a more serious one (e.g., tearing off a valve) 
results in a lowered mean blood-pressure. It is possible that 
nervous reflexes may play some part in maintaining the blood- 
pressure in these cases, especially when the injury to the valves 
is sudden. The principal factor, however, is undoubtedly the 
accommodation of the heart muscle itself. 

All our experience goes to prove that a muscle will hyper- 
trophy if it does an increased amount of work over a long 
period of time. We should expect the same rule to apply to 
individual parts of the heart, and especially so since their work 
is not limited to eight or ten hours a day, but is continuous, 
day and night. The work of the left ventricle is increased in 
aortic insufficiency, for it must propel not only the blood which 
enters from the auricle, but, in addition, that which leaks back 
from the aorta during each diastole. The total amount ex- 
pelled is therefore increased, while the pressure against which 
it is expelled is but little changed. Practical observations have 
shown that in aortic insufficiency there is always an hyper- 
trophy of the left ventricle with a dilatation of its cavity. The 
cavity is dilated on account of the abnormal amount of blood 
which it must accommodate, and the walls hypertrophy be- 
cause of the extra work thrown upon them. If the conditions 



38 CLINICAL PATHOLOGY 

for an increased pressure in the left auricle, as described above 
(p. 26), are present, then its work and the work of the right 
ventricle are also increased, and hypertrophy of these two parts 
of the heart results. 

Unfortunately we possess no exact anatomical data con- 
cerning these last points. The thickness of the heart wall at 
autopsy is greatly influenced by the condition of the heart when 
it stopped beating, whether it was in systole or diastole, so that 
we cannot judge from such measurements as to whether such 
slight hypertrophy as would occur in the left auricle and the 
right ventricle in cases of aortic insufficiency was present or 
not. Perhaps the employment of W. Miiller's method will 
throw more light on the subject. 29 

It is often erroneously stated that every aortic insuffi- 
ciency is accompanied by a considerable, and easily demon- 
strable, enlargement of the left ventricle. When the muscle is 
efficient, the degree of dilatation and hypertrophy is directly 
dependent upon the amount of blood which regurgitates from 
the aorta. If a third or fourth of the volume driven out leaks 
back, it necessarily leads to a considerable dilatation and hy- 
pertrophy. If, however, only a few cubic centimetres flow 
back, it is possible that the lesion can be readily diagnosticated 
clinically from the characteristic murmur, but that the hyper- 
trophy and dilatation of the left ventricle will be so slight that 
it is quite impossible for the physician to detect it by physical 
examination. 

Aortic Stenosis. — In stenosis of the aortic orifice the flow 
of blood from the left ventricle into the aorta is impeded. It is 
probable that under physiological conditions this orifice is not 
round and large during systole, but that it is encroached upon 
by the contraction of the muscle which surrounds it and which 
is an extension upward of the ventricular musculature. The 

28 W. Muller, Die Massenverhaltnisse des menschlichen Herzens, Ham- 
burg, 1884. 



THE HEART 39 

blood flows smoothly up to the contracted portion and then out 
into the wider aorta. Under ordinary conditions, the delicate 
semilunar valves are easily thrust aside. If, on account of dis- 
ease, they become stiff and rigid, then they hinder the escape of 
blood more or less. The ventricle must therefore work against 
a greater resistance. The prolongation of the ventricular 
systole, which may be from seven to thirty per cent, longer 
than normal, 30 is by no means proportionate to the increased 
resistance. The lesion, therefore, causes a greater amount of 
work to be thrown on the left ventricle. As a result of this 
extra work, we always find an hypertrophied left ventricle in 
cases of aortic stenosis. At first, there is no dilatation of its 
cavity, and the auricle, lungs, and right heart are entirely un- 
affected. A dilatation will only occur when the heart muscle 
can no longer accomplish the additional work, either because 
the obstruction has become too great, or because the muscle 
itself is weakened. 

Mitral Stenosis. — Lesions at the mitral orifice produce more 
complicated conditions than those at the aortic, because they 
lead to changes in the lungs and in the right heart. 

In mitral stenosis 31 there is a hinderance to the flow of 
blood from the left auricle into the left ventricle. When the 
auricle contracts, it must overcome a greater resistance, and 
this additional work leads to an hypertrophy of its muscula- 
ture. On account of the thin walls, however, its capacity for 
increased work is very limited, so that a dilatation occurs much 
earlier than in the case of the ventricle. An important factor 
contributing to this dilatation is the increased pressure which 
prevails in the pulmonary veins. At each systole of the auricle, 
an unusual proportion of its contents is forced back into the 
pulmonary veins owing to the obstruction in front at the mitral 
orifice. During diastole, therefore, the blood from the lungs 

80 Likleritz, Ztft. f. klin. Med., vol. xx. p. 374. 
" D. Gerhardt, Arch. f. cxp. Path., vol. xlv. p. 186. 



40 CLINICAL PATHOLOGY 

enters the auricle with more than ordinary force, the diastolic 
pressure in the auricle is increased, and, owing to the dimin- 
ished muscular tonus during this period, the cavity becomes 
dilated. 

The abnormal pressure in the pulmonary veins is trans- 
mitted through the short and relatively wide capillaries of the 
lungs to the pulmonary artery. Everything now depends upon 
the behavior of the right ventricle, which is placed in much the 
same position as is the left ventricle in a case of aortic stenosis. 
The pressure in the pulmonary artery must be maintained at a 
higher level than usual, in order to maintain the difference in 
pressure between the artery and vein, and consequently the 
flow of blood through the lungs. We recognize this increased 
pulmonary pressure clinically by the accentuation of the second 
pulmonic sound. The extra work necessitated by this high 
pressure is thrown upon the right ventricle and leads to its 
hypertrophy. 

The effect of mitral stenosis upon the left ventricle 
depends entirely upon the amount of blood that the lat- 
ter receives. When the stenosis is slight and the right heart 
maintains the necessary pressure in the pulmonary system, the 
left ventricle is not affected, for it receives its customary supply 
of blood. If, however, the right heart cannot compensate for 
the obstruction present, then the left ventricle is not filled to 
the normal amount, its work is diminished, and its muscle 
atrophies. This reasoning has been confirmed by the findings 
at autopsy. In pure mitral stenosis, the left ventricle is either 
normal or atrophied. If at times an hypertrophy of the left 
ventricle has been found, it is to be attributed to an associated 
mitral insufficiency, present or past. The two lesions are very 
frequently combined, and this naturally modifies the resulting 
anatomical changes. 

Mitral Insufficiency. — The conditions present in mitral in- 
sufficiency are very similar to those in mitral stenosis. A part 



THE HEART 41 

of the contents of the left ventricle is thrown back into the 
auricle during systole, and the degree of insufficiency may be 
measured by the amount of blood which takes this backward 
course. The lungs and the right heart are affected precisely 
as in the case of mitral stenosis. The left auricle becomes 
dilated and hypertrophied, the blood-pressure in the pulmonary 
system is raised, and the right ventricle must pump against 
an increased resistance. The amount of blood delivered may, 
indeed, be decreased, but not enough to neutralize the effects 
of the increase in pressure. The work of the right ventricle 
is therefore usually increased, and correspondingly we ordi- 
narily find an hypertrophy of this part of the heart at au- 
topsy. 32 

During diastole the blood flows into the left ventricle with 
unusual force, owing to the increased pressure in the auricle and 
the pulmonary veins. The amount that flows in must also 
be greater than normal if the body is to receive its customary 
supply of blood, for with each contraction of the left ventricle 
a certain proportion of its blood does not pass into the aorta, 
but is thrown back into the auricle. It is therefore necessary 
for the ventricle to pump more blood than usual, and we have 
no reason to believe that it does so against a lessened resistance, 
for the leak is hardly large enough to bring that about. The 
increased work performed by the left ventricle leads to its 
hypertrophy, a condition always present in mitral insufficiency. 
The ventricular cavity also becomes dilated owing to the 
larger quantity of blood which it receives during diastole. 
Thus, hypertrophy and dilatation of the left ventricle go hand 
in hand. The combination is of advantage not only in pro- 
pelling the blood, but probably also in drawing it from the 
auricle and from the lungs during diastole. 

Valvular Lesions of the Right Side of the Heart. — Valvu- 
lar lesions of the right side of the heart give rise to secondary 

H Moritz, Arch. f. klin. Med., vol. lxvi. p. 4_m. 



42 CLINICAL PATHOLOGY 

changes, very similar to those which take place on the left side 
under similar conditions. We must remember, however, that 
the musculature of the right ventricle is relatively weak, and 
that it is not capable of the same degree of accommodation as is 
that of the left ventricle ; furthermore, that there is no power- 
ful ventricle directly behind the tricuspid orifice to compensate 
for its disabilities. The valves of the right side of the heart 
are not infrequently diseased during the fetal period. Al- 
though the tricuspid valve is but rarely the seat of a verru- 
cose inflammation in later life, a relative insufficiency of the 
tricuspid orifice is no uncommon sequel to valvular disease 
of the left heart. Disease of the pulmonary valves, developing 
during adult life, is a great rarity. 33 

During fetal life, micro-organisms in the blood-stream 
usually injure the valves of the right side of the heart, whereas 
in extra-uterine life the left side is the one which is more fre- 
quently affected. One is tempted to explain this remarkable 
fact by the relative amounts of work done by the two sides 
or by the influence of aerated blood, since in fetaL life it is the 
right side which receives the aerated blood. We have no 
proof, however, for either of these two hypotheses. A fetal 
endocarditis is not uncommonly associated with congenital 
malformations, such as septum defects, transposition of the 
arteries, or persistence of the Ductus Botalli. Possibly the 
malformations diminish the resistance of the endocardium to 
infectious agents. The most important of the congenital heart 
lesions is pulmonary stenosis. This stenosis, which may be 
situated either in the neighborhood of the valves or at the 
conus arteriosus, leads to hypertrophy of the right ventricle 
precisely as an aortic stenosis leads to hypertrophy of the left. 

Combined Valvular Lesions — The effects of valvular dis- 
ease may be best studied when there is a simple stenosis or 
insufficiency of a single valve, and when no complications are 
83 Geigel, Munch, med. Wochens., 1897, No. 9. 



THE HEART 43 

present. Yet such simple cases are rare. In the right heart 
we frequently find associated defects in development; in the 
left heart, combinations of several valvular lesions. Pure 
mitral insufficiency is comparatively frequent, but uncompli- 
cated cases of mitral stenosis, or of aortic insufficiency, or of 
aortic stenosis, are much rarer than are the combinations of 
mitral insufficiency with mitral stenosis, aortic insufficiency 
with aortic stenosis, or aortic insufficiency with double mitral 
disease. The aortic semilunar valves are closely adjacent to 
the aortic segment of the mitral valve, and when the latter is 
diseased the former are also frequently affected. 

The effect of a combination of valvular lesions is the re- 
sultant of the effects of the individual lesions. They may even 
tend to neutralize each other, so that the combination is less 
harmful than the individual lesions. For example, the dilata- 
tion of the left ventricle resulting from aortic insufficiency 
may be lessened by an associated aortic stenosis ; and although 
both mitral insufficiency and mitral stenosis produce similar 
effects in damming the blood back into the lungs, they tend to 
neutralize each other so far as their effect upon the left ven- 
tricle is concerned. Indeed, we may say in general that the 
stenosis which so often follows a valvular insufficiency may be 
of advantage in that it may limit the amount of blood which 
regurgitates. Caution must be used, however, in deciding this 
question in the individual case, for other factors, especially the 
condition of the heart muscle, are often of paramount im- 
portance. 

Hypertrophy of the Right Ventricle. — The work of the 
right ventricle is directly dependent upon the condition of the 
pulmonary circulation. Anything that increases the pressure 
in the pulmonary vessels increases the resistance against which 
the right ventricle must force the blood. We have seen an 
illustration of this in the case of mitral valve disease. Similar 
effects may result from a weakened left ventricle which can- 



U CLINICAL PATHOLOGY 

not completely empty itself during systole. Its power of 
suction in early diastole is also diminished, for this power de- 
pends upon the elastic rebound after a powerful contraction, 
or possibly upon an active process in the muscle-fibres them- 
selves. 34 The unexpelled blood in the ventricle and the lessened 
suction hinder the entrance of blood from the lungs, raise the 
pressure in the pulmonary circulation, and so increase the work 
of the right ventricle. We have seen that the left ventricle can 
alter its elasticity under certain circumstances so that it can 
hold a larger amount of blood in each diastole, and the ques- 
tion naturally arises, Why does not the weakened ventricle do 
this instead of damming the blood back into the lungs? The 
reason seems to be that the muscle tissue is so diseased that 
its elasticity as well as its contractility is diminished. 

Primary disturbances of the circulation in the lungs may 
likewise affect the right heart. We know that the resistance to 
the blood-flow in the pulmonary vessels is normally very slight. 
Large vascular areas, up to three-quarters of the total, may be 
thrown out of function, and yet a sufficient amount of blood 
may be sent through to the left ventricle. 35 The right heart 
simply propels the blood through the remaining pulmonary 
vessels at a higher rate of speed. The open vessels are, in- 
deed, dilated, but not sufficiently to compensate for the others 
thrown out of function, so that the pressure in the pulmonary 
artery rises. The dilatation of the vessels remaining open is 
quite different from that which takes place under correspond- 
ing circumstances in the greater circulation. In the latter, 
when a vessel is closed, the general pressure does not neces- 
sarily rise, because vasomotor influences may produce a com- 
pensatory vascular dilatation in other parts of the body; in 
the lungs, the resulting dilatation is purely passive, and is 
due to the increase of pressure in the pulmonary artery caused 

34 Brauer, Kongress f. inn. Med., 1904. 

35 Lichtheim, Die Storungen des Lungenkreislaufes, Berlin, 1876. 



THE HEART 45 

by the obstruction in one of its branches. This increased 
pressure necessitates an increase in the amount of work done 
by the right ventricle, which will be greater or less in any 
given case, depending upon the number and dilatability of the 
pulmonary vessels remaining open. In case the increased 
work persists for some time, hypertrophy of the right ven- 
tricle will ensue. 

For this reason the right ventricle becomes hypertrophied 
as a result of sclerosis of the pulmonary artery (a rare condi- 
tion) ; 36 also in those more frequent pulmonary diseases 
which lead to destruction or compression of the vessels, such 
as cirrhosis of the lungs from various causes, chronic pneu- 
monia, pulmonary emphysema, and thoracic deformities. 37 
Long continued bronchitis is often described as a cause of 
hypertrophy of the right ventricle, and especially as a cause of 
the enlarged right heart found in children, who are subjects of 
this disease. It is difficult to say whether the bronchial inflam- 
mation directly increases blood-pressure or whether the con- 
tinual coughing gives rise to the hypertrophy of the right ven- 
tricle by its effect on the intrathoracic pressure. 

It has often been asserted that we have in tuberculosis an 
exception to the general rule that chronic pulmonary disease 
leads to hypertrophy of the right ventricle. To account for 
this supposed exception, numerous explanations have been 
offered, one of which is to the effect that the total quantity of 
blood is diminished in this disease. We now know, however, 
that tuberculosis is no exception to the general rule. Ana- 
tomical investigations have shown that, in proportion to the 
body weight, the weight of the right ventricle is increased in 
a large proportion of those who die of consumption. 38 Clini- 
cal evidence supports the same view, for it is not uncommon 

30 Romberg, Arch. f. klin. Med., vol. xlviii. p. 107. 
" Hirsch, ibid., p. 328. 
" Hirsch, \<>c. cit. 



46 CLINICAL PATHOLOGY 

to find an accentuation of the second pulmonic sound during 
life in tuberculous patients. 

Extensive pleuritic adhesions may also lead to an hyper- 
trophy of the right ventricle. 39 Their interference with the 
movements of the lungs doubtless deprives the pulmonary 
circulation of the assistance usually derived from these 
movements, so that additional work is thrown on the right 
ventricle. 

Hypertrophy of the Left Ventricle. — The work of the left 
ventricle is made greater by any increase in the resistance to the 
flow of blood through the peripheral arteries. A temporary 
increase in resistance, arising from vasomotor influences, is 
not an uncommon physiological occurrence. 

Of considerable importance as a cause of permanent in- 
crease in the arterial pressure are certain forms of arterio- 
sclerosis. 40 When the elasticity of the arteries is diminished, 
they offer a greater resistance to dilating forces ; but once hav- 
ing been dilated, they do not so easily recover their original 
size. 41 Various opposing factors must therefore be considered. 
The rigidity of certain areas may be neutralized by dilatation 
of other areas. There is also a tendency for the affected ves- 
sels to become permanently dilated. The precise effect of these 
various opposing factors can only be determined by experi- 
mental investigations. Hitherto we have had no method of 
experimentally inducing the disease, but since arteriosclerosis 
has recently been produced by the injection of adrenalin chlo- 
ride into animals, 42 we may expect important developments in 
this field of research in the near future. 

As a matter of fact, hypertrophy of the left ventricle de- 
velops in only a small proportion of patients with uncom- 

89 Baumler, Arch. f. klin. Med., vol. xix. p. 471. 

40 Kongress f. inn. Med., 1904. 

" Israel, Virch. Arch., vol. ciii. p. 461. 

42 W. Erb, Kongress f. inn. Med., 1904. 



THE HEART 47 

plicated arteriosclerosis. It is present especially in cases of 
sclerosis of the first part of the aorta, and in extensive sclerosis 
of the splanchnic vessels. 43 The splanchnic arteries are of 
such paramount importance in controlling the peripheral re- 
sistance that when they are diseased it is difficult or impossible 
to attain compensation by a dilatation of other vascular areas. 
Other uncomplicated cases of arteriosclerosis rarely show any 
marked degree of heart hypertrophy. 

Various complications often render it extremely difficult to 
estimate the effect of arteriosclerosis upon the heart. The same 
cause that induces the disease of the arterial walls may also in- 
dependently act upon the heart muscle. As examples of such 
causes, we may name the excessive use of alcoholic drinks, of 
coffee, and of tobacco, severe and continued exertion, infec- 
tious diseases, and, above all, syphilis. Then, too, arteriosclero- 
sis itself may lead to degeneration of the heart muscle owing 
to an involvement of the coronary arteries. Finally, an asso- 
ciated chronic nephritis may produce an hypertrophy of the 
heart. We thus see how extremely difficult it is, in an indi- 
vidual case, to determine whether the arteriosclerosis is the 
direct cause of the heart hypertrophy or whether the latter is 
due to some associated complication. 

The left-sided hypertrophy accompanying aneurism of 
the aorta is to be ascribed to some complicating condition. It 
is difficult to see how a dilatation of the vessel would increase 
the work of the heart, and, as a matter of fact, we do see 
patients with aneurisms in whom there is no enlargement of 
the left ventricle. When the latter occurs, we may usually 
ascribe it to the arteriosclerosis present or to an associated 
aortic insufficiency. 

Hypertrophy of the left ventricle may result from that rare 
condition, congenital stenosis of the aorta. Such a narrowing 
would increase the work of the heart by offering a greater 
" Romberg and Hasenfeld, Arch. f. klin. Med., vol. lix. p. 193. 



48 CLINICAL PATHOLOGY 

resistance to the blood-flow. In this condition, the hypertrophy 
may not develop until late in life. If such be the case, we 
may assume that the stenosis produced but little effect so long 
as there were no great demands upon the heart, but that the 
hinderance made itself felt when a more active circulation was 
rendered necessary by the exertion of later life. 

Severe dyspnoea causes a marked rise in blood-pressure, 
and it has long been a question whether moderate dyspnoea 
continued over a long period of time may not give rise to 
hypertrophy of the left ventricle. From recent observations, 44 
we know that persons with such chronic dyspnoea do show an 
unusually high arterial pressure, and there is reason to believe 
that this may ultimately produce an hypertrophy of the left 
ventricle. 

Hypertrophy of Both Ventricles. — Hypertrophy of both 
ventricles is produced by causes that increase the work of both. 
Pericardial adhesions with mediastinitis are usually reckoned 
among such causes, and it is easily conceived that these condi- 
tions might throw extra work upon the heart, which must now 
move surrounding structures, even the chest wall, with each 
contraction. As a matter of fact, we frequently find heart 
hypertrophy associated with chronic pericarditis. It is, how- 
ever, questionable whether any causal relation exists between 
the two, for in some cases no hypertrophy is present, and, 
indeed, the heart may be atrophied. Since pericarditis is often 
associated with disease of the heart muscle, the cases that show 
hypertrophy should be studied with especial regard for the 
effect which these myocardial changes may have had in the 
production of the hypertrophy. 

It is theoretically possible that an increase in the number of 

beats per minute might lead to hypertrophy of the heart. Such 

an increased heart-rate is seen in nervous people, especially 

in association with exophthalmic goitre. We often have the 

" Hensen, Arch. f. klin. Med., vol. lxvii. p. 479. 



THE HEART 49 

impression that the heart contractions are also more forcible 
in this disease, and it has been shown that the blood-press- 
ure is frequently above the normal. 45 The conditions neces- 
sary to produce an hypertrophy are therefore present, and, as 
a matter of fact, it is not uncommon to find enlargement of 
the heart accompanying exophthalmic goitre. It is, however, 
questionable whether this hypertrophy is due to the rapid heart 
action or whether it is due to the direct action of toxic sub- 
stances. In some cases of rapid heart action, the hypertrophy, 
if present at all, is very slight, probably because the rapid 
beating does not continue for any length of time. 

Cardiac Changes in Renal Disease. — The changes in the 
heart that follow disease of the kidneys are very difficult to 
explain. In a great number of cases of acute and chronic 
nephritis there is an increase in the arterial pressure. If this 
increase in pressure lasts for more than four weeks, an hyper- 
trophy of the heart develops. 46 It follows, therefore, that 
heart hypertrophy occurs more frequently in chronic than in 
acute nephritis. In the endeavor to explain this rise of pressure 
and the concomitant hypertrophy, we must first know what 
parts of the heart are affected. According to v. Bamberger's 
statistics, 47 the left ventricle alone is enlarged in about half 
the cases, while in a somewhat smaller number both ven- 
tricles are involved. These figures, however, are based upon 
the apparent size of the heart or upon measurements of the 
thickness of the muscular wall, disregarding the question as 
to whether the heart stopped in systole or diastole and dis- 
regarding also the relation of the size of the heart to the 
total weight of the body. Accurate figures can only be ob- 
tained by weighing the different parts of the heart accord- 
ing to the method of W. Muller. In fourteen cases of chronic 

"HochhatlS, Deut. med. Wochens., 1900, No. 44. 
" Friedlander, Arch. f. Phys., 1881, p. 168. 
" Volkmann's klin. Vort.. No. [73. 
4 



50 CLINICAL PATHOLOGY 

nephritis studied by this method 48 every portion of the heart, 
auricles and ventricles, were found hypertrophied, in the great 
majority of cases, the left ventricle being most affected. These 
observations, in spite of the small number of cases, are of great 
value on account of their accuracy. Clinically we frequently 
hear an accentuation of the second pulmonic sound in cases 
of chronic nephritis, an indication of increased pressure in the 
pulmonary circulation which would ultimately result in hyper- 
trophy of the right ventricle. 

Not all diseases of the kidney induce heart hypertrophy. 
It is frequently absent in the nephritides produced by toxic 
agents, such as arsenic and phosphorus, and in those associated 
with certain infectious diseases, as diphtheria and typhoid fever. 
In primary acute Bright's disease, which is probably infectious 
in character, and in the nephritis secondary to scarlet fever, 
there is practically always an increase in the arterial pressure. 
Chronic interstitial nephritis is always accompanied by an en- 
largement of the heart, frequently of the most extreme grade. 
In the so-called chronic parenchymatous nephritis, hypertrophy 
of the heart is present in about half the cases. 49 There are no 
changes in the heart in pure cases of amyloid kidney. It is 
important to note that when obstruction to the flow of urine 
leads to renal disease, as from calculi or abdominal tumors, 
the heart frequently undergoes hypertrophy. 

Any attempt to explain the heart hypertrophy that accom- 
panies diseases of the kidney must start from the fact that there 
is an increased arterial pressure. This appears before the 
hypertrophy. A rise of blood-pressure, amounting to fifty 
millimetres of mercury, has been observed within forty-eight 
hours after the onset of an acute nephritis. 50 The accentua- 

4S Hasenfeld, Arch. f. klin. Med., vol. lix. p. 210; Hirsch., ibid., vol. 
Ixviii. p. 74. 

*• Buttermann, Arch. f. klin. Med., vol. lxxiv. p. I. 
60 Buttermann, loc. cit. 



THE HEART 51 

tion of the second pulmonic sound in many cases allows us to 
infer a corresponding rise of pressure in the pulmonary cir- 
culation. As has already been stated, this inference is borne 
out by anatomical investigations, for in eighty-two per cent, of 
cases examined by modern methods, hypertrophy was present 
in all divisions of the heart, and in the fourteen per cent., in 
which only the left ventricle was apparently affected, so much 
cedema was present that a slight hypertrophy of the right side 
of the heart might not have been demonstrable on account of 
the great weight of the body. It is possible that the hyper- 
trophy of the left ventricle is more pronounced in the early 
stages of nephritis, and that it extends to the rest of the heart 
later. At any rate in the great majority of cases of chronic 
nephritis, the heart, if affected at all, is affected in its entirety, 
and any explanation of the cause of the hypertrophy must take 
this fact into consideration. 

One view held is that the left ventricle is primarily affected 
and the rest of the heart is only secondarily involved. The 
older explanations of such a condition — viz., that it is due to 
the increased filling of the coronary arteries or the intimate 
connection between the two sides of the heart — are absolutely 
without foundation. Another possibility — viz., that an in- 
competency of the left ventricle leads to general hypertrophy 
of the heart — is not so easily discovered, and needs further 
investigation. With the present data, however, I am disin- 
clined to accept such an explanation. 

What causes the hypertrophy of the heart and the increase 
in arterial pressure? Two possibilities present themselves, — 
a primary increase in the activity of the heart or a primary 
rise in the peripheral resistance. We have no grounds for 
believing that the former possibility plays any great part in 
the causation of the heart hypertrophy of nephritis. In un- 
complicated cases, the rate of the heart is not changed, the 
amount of blood propelled at each beat is not increased, for 



52 CLINICAL PATHOLOGY 

no dilatation of the ventricles exists, and it has not been shown 
that the blood is expelled from the ventricle at a higher rate 
of speed ; i.e., the period of systole is not shortened. Even 
were there a primary increase in the heart's activities, it would 
not be clear why the arterial pressure should be raised, for a 
dilatation of the vessels might counteract any such effect, as 
probably does happen in some cases of exophthalmic goitre. 

The second possibility, that the rise of pressure is due to in- 
creased peripheral resistance, seems almost certain. According 
to Cohnheim's famous theory, the inflammation of the kidney 
opposes a resistance to the flow of blood through it, and in 
order to increase this flow the general blood-pressure is raised 
by a general contraction of the arterioles outside of the 
kidney. This theory is no longer tenable, because it fails to 
explain the hypertrophy of the right ventricle and because of 
other purely physiological reasons. A general decrease in the 
caliber of the blood-vessels would explain everything, for even 
a slight diminution, either in all the vessels or in the more 
important vascular areas, would greatly increase the work of 
the heart, since this varies inversely as the fourth power of the 
diameter of the combined vessels. Such a change of diameter, 
if present, must take place within a short space of time, as in 
acute nephritis; and must last for years, as occurs in chronic 
interstitial nephritis. Furthermore, it must affect both the 
general and the pulmonary vessels. Although a contraction of 
the smooth muscle of the smaller arteries might well explain the 
rise of pressure in acute nephritis, it is hardly conceivable that 
this should be maintained during the long course of a chronic 
nephritis. On the other hand, inflammatory processes might 
lead to a permanent narrowing of the blood-vessels. Such in- 
flammations have, in fact, been described, 31 yet the findings are 

"Johnson, Med-chir. Trans., vols, xxix., xxx., xxxiii., xlii., and li. ; 
Gull and Sutton, ibid., vol. xxxiii. ; Sotnitschewsky, Virch. Arch., vol. 
lxxi. p. 453. 



THE HEART 53 

inconstant and they have frequently been missed in acute 
nephritis, even though heart hypertrophy was present. 

Finally, as a cause of the heart hypertrophy, we might 
conceive that an increased friction in the flow of blood would 
produce a rise of blood-pressure. Here, again, direct observa- 
tions fail to support the theory ; nephritic blood does not show 
a greater viscosity than normal blood. 52 

No explanation, therefore, thus far given for the heart 
hypertrophy accompanying renal disease, is free from objection. 
Personally I am inclined to locate the primary cause of the in- 
creased pressure in changes affecting the blood-current in the 
smaller arteries, and I should recommend a renewed study of 
these vessels, especially in cases of acute nephritis. Minimal 
changes here might entail serious consequences, for, as has been 
said, the work of the heart varies inversely as the fourth power 
of the diameter of the vessels. 53 

The ''Athlete's Heart." — As has been previously stated, 
severe muscular exertion ordinarily increases the weight of the 
heart in the same ratio as it increases the weight of the general 
musculature. It is frequently assumed, however, that hyper- 
trophy of the heart may result from prolonged muscular exer- 
tion. Such a relative increase in the heart's weight does per- 
haps occur in individual cases without there being any 
impairment of function, but this is certainly exceptional (see p. 
30.) When overactivity affects the heart, it usually does so 
by causing a primary weakness of the muscle; yet here again 
it may be frequently questioned whether this weakening should 
not be attributed rather to some other associated causal agent, 
such as the excessive use of alcoholic liquors, arteriosclerosis, 
or renal disease. Further observations upon these questions 
are therefore necessary. 

"Hirsch and Beck, Arch. f. klin. Med., vol. lxix. p. 503; vol. lxxii. 
p. 560. 

M Lewy, Pfliiger's Arch., vol. lxv. p. 47. 



54 CLINICAL PATHOLOGY 

The " Beer Heart." — It is not uncommon to find weak 
hearts with an hypertrophy of the muscle and a dilatation of 
the cavities in men who have been accustomed to drink very 
large quantities of beer. Such hearts are most frequently 
seen in Munich, 54 and may show extreme grades of hyper- 
trophy. Excessive wine-drinkers occasionally suffer from a 
similar condition, whereas drinkers of more concentrated alco- 
holic liquors are only very rarely affected in this way. 55 They 
tend to develop cardiac weakness unassociated with hyper- 
trophy. In many beer-drinkers no other etiological factor is 
present except the immoderate use of beer. The majority, 
however, do very heavy work and consume large quantities 
of food in addition to their beer. Some also have diseased 
kidneys, although we are not yet certain as to whether these 
are secondary to the hypertrophy of the heart or not. 

The cause of the enlargement of the heart in beer-drinkers 
has been ascribed by some to an increase in the total amount 
of blood, a genuine plethora. 56 A larger amount of blood, 
however, does not necessarily produce a rise in arterial 
pressure. It is claimed by others that the quantity of blood 
thrown out at each systole is increased in these patients, 57 and 
that this increases the heart's work. Such an explanation has 
much in its favor, but we cannot regard it as established, espe- 
cially since not all beer-drinkers acquire a heart hypertrophy. 
Personally I have observed these heart changes in brewers, 
laborers, and students who drank immoderately, and who also 
did heavy work or took violent exercise. A number of such 
people certainly give the impression of being " full-blooded." 
It seemed to me that the combination of beer-drinking with 



64 Bollinger, Arbeiten aus dem path. Institut zu Munchen, 1896 ; Rieder, 
Arch. f. klin. Med., vol. lv. p. 8. 

"Aufrecht, Arch. f. klin. Med., vol. lvi. p. 615. 

06 Bollinger, loc. cit. 

m Tigerstedt, Skan. Arch. f. Phys., vol. iv. p. 241. 



THE HEART 55 

heavy work is responsible for the heart condition. One gets 
the impression, furthermore, that both the dilatation and the 
hypertrophy may disappear if the patient changes his manner 
of living. 

Gourmands may at times acquire a similar heart condition 
probably from the large amounts of food and of wine, the 
heavy smoking, and the not infrequent sexual excesses. In 
such cases the picture is often complicated by arteriosclerosis, 
nephritis, and myocarditis. 

The Heart in Pregnancy. — It has been frequently asserted, 
especially by French observers, that there is an enlargement of 
the heart during pregnancy. As a matter of fact, in pregnancy, 
as in other conditions associated with a high position of the dia- 
phragm, the area of cardiac dulness is enlarged because the 
heart approaches the chest wall. It has, however, been proved 
with all certitude that pregnancy exercises no effect on the 
heart other than that which could be explained by the general 
increase in the weight of the body. 58 

The Ability of the Heart to Hypertrophy. — It may be 
asked, what conditions influence the power of the heart to 
hypertrophy? We may mention three factors. In the first 
place, the rapidity with which new demands are made on the 
heart. If, as usually occurs, the work is gradually increased, 
then the heart has time to hypertrophy gradually and to attain 
ultimately an enormous size and greatly increased working 
capacity. In the second place, the degree of hypertrophy is 
influenced by the amount of new work required. The more 
work the heart does, the greater is the resulting hypertrophy. 
As has been said, tin enormous increase in work may be ac- 
complished, provided the new demands are gradually increased. 
Yet even sudden calls upon the healthy heart are well responded 
to up to a certain limit. We can give no definite figures for 
this limit in man, but wc know from clinical experience that it 
68 Hirsch, Arch. f. klin. Med., vol. Ixiv. i>. 597. 



56 CLINICAL PATHOLOGY 

is not a low one. Experimentally it has been shown that the 
heart of a large healthy dog is able to pump six times the cus- 
tomary quantity of blood, and to overcome three times the 
usual blood-pressure. 

The third and most important factor that influences the 
heart's capacity to hypertrophy is the condition of the cardiac 
muscle. Without a healthy muscle, the heart cannot accommo- 
date itself to an increase in work. The general nutrition of 
the body is of comparatively little significance, for Tangl 59 
has shown that, even in the most emaciated animals, hyper- 
trophy of the left ventricle will develop after an artificial valvu- 
lar lesion. We have no right, therefore, to attribute a lack 
of hypertrophy to the poor general nutrition of the patient. 
It is to be attributed solely to the fact that there has been no 
increase in the heart's work. When additional work is re- 
quired of the heart, there are only two possibilities, — either it 
responds and hypertrophies, or it weakens. It is, of course, 
probable that when the body is well nourished the heart is 
better able to respond, and is less likely to weaken. We may 
mention here that in childhood the heart possesses far greater 
powers of adaptation than in later life, and that it is then able 
to compensate to a very marked degree. 

Concentric and Eccentric Hypertrophy. — The heart hy- 
pertrophies, discussed thus far, may be divided into two gen- 
eral classes, according to the size of the ventricular cavities. 
When the muscle increases without any enlargement of the 
cavity, we speak of a simple (concentric) hypertrophy. On 
the other hand, the size of the cavity may also increase, 
and such a condition is called an eccentric "hypertrophy. This 
division is applicable only to hearts which are properly main- 
taining the circulation. As soon as they fail in this, dilata- 
tion of a totally different nature occurs, which shall be dis- 
cussed later. 

09 Virch. Arch., vol. cxvi. p. 432. 



THE HEART 57 

The ventricular cavity must become dilated during diastole 
whenever it is necessary to pump more blood at each beat. 
Whether the cavity is also dilated in systole or not, depends 
upon the completeness with which the ventricle empties itself. 
Experimental evidence would lead us to the belief that an in- 
complete expulsion of the blood is by no means infrequent. In 
heart-failure this is the rule, and even when the heart is main- 
taining a good circulation it does not empty itself completely 
when very large amounts of blood must be propelled, or when 
the resistance is much increased. 60 

So long as compensation is good, it is rare for the right 
ventricle to become dilated as a result of increased pressure 
in the pulmonary circulation. The same is true of the left 
ventricle in cases of arteriosclerosis and nephritis. In other 
words, the hypertrophy in these conditions is usually of the 
concentric variety. On the other hand, the hypertrophy re- 
sulting from aortic or mitral regurgitation, from excessive 
exertion, or from the immoderate use of beer, is usually asso- 
ciated with dilatation of the cavity; it is an eccentric hyper- 
trophy. It is necessary to be rather guarded in our judgment 
of the two latter groups of cases, for they are not usually seen 
until compensation has become broken. 

The Inefficiencies of a Compensated Circulation.— The hy- 
pertrophy which enables the heart to carry on the circulation 
under pathological conditions is spoken of as a compensatory 
hypertrophy. This does not mean that the new circulatory 
mechanism is just as effective as the old. According to the 
view of Romberg and of the author, however, the power of the 
hypertrophied heart muscle to accommodate itself to further 
new demands is equal to that of the intact muscle. 01 An illus- 
tration will show what complex factors are involved in the 
consideration of this problem. Romberg has shown that ani- 

•°See Roy and Adami, Brit. Med. Jour., 1888, vol. ii. p. 321. 
"Romberg and Hasenfeld, Arch. f. exp. Path., vol. xxxix. p. 333. 



58 CLINICAL PATHOLOGY 

mals with an aortic insufficiency are capable of overcoming 
increased resistance, produced by compression of the aorta, 
for as long a time and with as little fatigue as are normal 
animals. During the earlier period of increased resistance, 
however, their blood-pressure is not maintained at so high a 
level, and the more severe the insufficiency the lower is the 
blood-pressure. Yet this effect cannot be attributed to a dimin- 
ished power of accommodation in the hypertrophied muscle. 
The increased resistance, raising the blood-pressure, causes 
more blood to leak back into the ventricle during diastole, so 
that the left ventricle has two unfavorable factors to contend 
with, increased resistance and a greater leak in its valves. The 
accommodative power of the muscle, therefore, would have to 
be greater than that of the normal muscle to overcome an 
equal rise of blood-pressure. If we compare the behavior of 
a heart sustaining a recent aortic insufficiency where there is 
no hypertrophy, with one that has had time to hypertrophy, 
then the greater reserve force of the latter is well shown 
under the conditions of Romberg's experiment. It seems to 
us probable, therefore, that the hypertrophied heart muscle 
possesses the same amount of reserve force as the normal 
muscle. 

And yet, as has been stated, a compensatory enlargement 
of the heart cannot restore the circulation to a normal condition, 
and for many reasons. In the first place, the blood-pressure 
in the pulmonary system must frequently be maintained at 
a higher level than usual, as happens in many diseases of the 
left heart and of the lungs (see p. 43). If the high pressure 
in the pulmonary circulation continues for any length of time, 
the connective tissue of the lungs increases and small quanti- 
ties of blood are extravasated. The resulting pigment is taken 
up by the alveolar epithelial cells, and if these appear in the 
sputum they are diagnostic of chronic passive congestion of 
the lungs. These changes in the pulmonary tissues undoubt- 



THE HEART 59 

edly interfere with the proper aeration of the blood. The 
increased pressure in the pulmonary system likewise interferes 
with breathing. We have no good explanation of the manner 
in which it does this. Neither the older view that the swollen 
and tortuous capillaries limit the space in the alveoli, nor the 
more modern explanation that the lungs become swollen and 
inelastic, 62 has received general acceptance. The tissues of a 
lung that is the seat of chronic passive congestion also seem 
to suffer in nutrition and in resistance to infection. At least, 
such patients are very susceptible to bronchitis, so that it seems 
as if the lungs had become less able to resist organisms that may 
have entered through the upper air-passages. Thus we see that 
a cardiac lesion, even though compensated, may seriously inter- 
fere with the functional capacity of the lungs. 

Lesions of the right side of the heart not infrequently 
lead to stasis in the veins of the general circulation. Since 
the same condition is produced by any weakness of the right 
ventricle, it will be considered in that connection. 

All patients with continuously high arterial pressure are 
in danger of rupture of an artery, which is especially true if 
the walls of the arteries are already weakened. The imme- 
diate cause of the hemorrhage is usually some act which itself 
produces a further rise in pressure, such as excitement, violent 
exertion, coitus, and straining at stool. In patients with arte- 
riosclerosis or granular kidney, such acts are not infrequently 
followed by hemorrhages into the brain or retina. 

As is well known, the characteristic pulse of aortic insuffi- 
ciency is one of great excursion. It bounds up against the 
palpating finger, and as suddenly recedes. It may be trans- 
mitted to the capillaries, producing a visible capillary pulse. 
Such a pulse is not without its effect upon the arterial wall. 
The rapid and excessive distention may result ultimately in 
a stretching of the artery, so that vasomotor influences are 
" v. Basch, Kongr. f. in. Med., 1889, p. 384. 



60 CLINICAL PATHOLOGY 

no longer able to reduce it to its former size. The amount of 
blood in the body is limited, and, since the dilated arteries 
contain more blood than normally, there may thus result an 
inadequate filling of the rest of the vascular system. This is 
perhaps the explanation of the poor circulation sometimes seen 
in cases of aortic insufficiency in which there is no weakening 
of the left ventricle. 

Still another effect of an enlarged heart must be men- 
tioned, — viz., the space taken up in the chest cavity and the 
resultant compression of the other intrathoracic organs. 

We have dealt thus far with the heart's condition so long 
as the body is at rest. If patients with heart disease exercise, 
the work of the heart is at times enormously increased. We 
have already described how an increased peripheral resistance 
affects the work of a heart with an aortic insufficiency, not 
only by raising the pressure against which it must pump the 
blood, but by increasing the amount that regurgitates during 
each diastole (p. 58). Similar relations hold good for other 
valvular lesions. 63 

Thus we see that, although the hypertrophy of the heart 
may compensate for the valvular lesion in certain particulars, 
it cannot restore the circulatory conditions to their normal 
state. 

Myocardial Changes in Hypertrophied Hearts. — And yet 
the chief source of difficulty with an hypertrophied heart does 
not lie in any of the factors thus far mentioned, but rather in 
the condition of the muscle itself. We have taken great pains 
to show that a healthy hypertrophied muscle possesses capa- 
bilities not differing from those of the normal muscle. The 
hypertrophied heart muscle and the enlarged biceps of the 
athelete are comparable in some cases, but, unfortunately, it 
is not so in the majority of instances. For the very causes 
which lead to hypertrophy of the heart frequently, at the same 
e3 Levy, Ztft. f. klin. Med., vol. xxxi. p. 521. 



THE HEART 61 

time, produce pathological changes in the myocardium. It will 
be recalled how frequently the infectious diseases give rise to 
valvular lesions and consequently to heart hypertrophy. In 
such infections the myocardium is almost invariably diseased, 
and often to a greater degree than the endocardium. These 
diseases, and especially acute articular rheumatism, cause de- 
generations of the muscle fibres, interstitial myocardial inflam- 
mations, and diseases of the arteries. 64 It cannot be doubted 
that these disturb the functions of the heart muscle most 
seriously. Such a disturbance may take the form of an acute 
dilatation, which is not of a compensatory nature, due to the 
necessity for an increased supply of blood, but which results 
from the incomplete contractions of the heart muscle. The 
dilatation of the right ventricle in the early stages of a mitral 
lesion is usually of this nature. Chronic myocardial changes 
are likewise of great importance in the subsequent course of a 
valvular disease. They show a tendency to spread gradually, 
leaving behind them connective tissue scars instead of healthy 
muscle-fibres. There is therefore not only a destruction of 
muscle, but a resulting scar tissue, which undoubtedly hinders 
the activities of the healthy muscle-fibres that remain. 

This is the real cause of weakness in many hearts where 
valvular disease has been diagnosticated. The myocarditis in 
such hearts has been frequently demonstrated. It is not neces- 
sarily present, it may vary both in location and intensity, 
and it bears no definite relation to the kind or age of the 
valvular lesion. It adds an uncertainty to the prognosis of 
valvular disease, which must always be taken into account. 
The progressive character of the processes in question is an- 
other source of uncertainty. On the one hand, the endocarditis 
may gradually progress and lead to more and more extensive 
alterations in the valves; while, on the other hand, the heart 
muscle may gradually weaken so that it becomes less and less 
"Albrccht, Der Herzmuskcl, II. Toil. 



62 CLINICAL PATHOLOGY 

able to respond to the increased calls made upon it. A most 
unhappy combination ! 

The weakness of the hypertrophied heart muscle in other 
conditions is less easily explained. Hypertrophy of the right 
ventricle often arises from diseases of the lungs. The progres- 
sive character of the pulmonary disease may gradually throw an 
overwhelming burden upon the right ventricle. In other cases, 
however, no such explanation is possible, and we are entirely 
ignorant of the reason why the hypertrophied ventricle 
weakens. 

So far as the left ventricle is concerned, the relations are 
comparatively simple when the hypertrophy arises from an 
arteriosclerosis, for it is well known that the coronary arteries 
are frequently involved in this process and that coronary 
sclerosis leads to most serious disturbances in the nutrition of 
the heart muscle. 

The hypertrophied hearts of patients with nephritis are oft- 
times singularly free from signs of weakness. Many patients 
with granular kidneys maintain a good circulation for years, 
and only in the last stages of the disease do they develop signs 
of cardiac weakness. Albrecht 65 has recently shown that, in 
such cases, disease of the myocardium, sufficient to explain all 
symptoms, is present. 

It is extremely difficult to explain the cardiac weakness 
that develops as a result of the misuse of beer and wine. 
In a number of these cases, the extensive fatty degeneration 
and the fresh inflammatory processes are, however, sufficient 
to account for all the symptoms. 66 It seems as if such hearts 
show less resistance to the causes which produce inflammation. 
The alcohol itself can hardly be the immediate cause of the 
inflammatory condition, for we know that large quantities of 
concentrated spirits may be taken without producing any such 

65 Der Herzmuskel, II. Teil. 

66 Krehl, Arch. f. klin. Med., vol. xlviii. p. 414. 



THE HEART 63 

changes in the heart muscle. It is, indeed, true that we are 
unable to positively deny the possibility that alcohol is the sole 
causative agent in these cases, especially since it is notoriously 
liable to produce similar changes in other tissues ; yet to us it 
seems more probable that the poison simply prepares the way 
for the infectious process. No satisfactory explanation can be 
given of those cases in which there is cardiac weakness with- 
out demonstrable signs of disease in the myocardium, and 
further studies are necessary to throw light on such conditions. 

We can now understand how it is that in many instances 
the hypertrophied heart is less efficient than the normal organ. 
Hypertrophy itself does not necessarily entail any weakness. 
Theoretically the hypertrophied organ possesses the same re- 
serve force as the healthy one. Such favorable hypertrophies 
are, indeed, observed, but unfortunately they are rare. In the 
majority of cases the cause which induces the hypertrophy also 
damages the capabilities of the muscle. The heart is so injured 
that it cannot properly respond to an emergency at the very 
time when its power to do so is most needed. 

For this reason, many hypertrophied hearts are unable to 
meet any additional call made upon them. They tire much 
more readily than the normal organ, and when once tired they 
do not recover so quickly. Indeed, a serious or even irrep- 
arable damage may result. On this account, the patient with 
heart disease is repeatedly warned of the dangers of over- 
exertion. On this acount, also, women who have heart disease 
often do badly during a confinement. 

Causes of Broken Compensation in Hypertrophied Hearts. 
— If a heart becomes unable to meet the increased demands that 
are made upon it, we speak of a break of compensation. This 
failure in compensation may be brought about in several ways. 
In the first place, what is ordinarily a moderate call upon the 
heart may be an excessive one in certain forms of disease. We 
have already shown, for example (p. 58), that in aortic insuf- 



64 CLINICAL PATHOLOGY 

ficiency a rise in peripheral resistance increases the work of 
the heart, not only by raising the pressure against which it 
must pump the blood, but by actually increasing the leakage 
backward into the ventricle during diastole. Even though 
the accommodative power of the muscle were normal, it might 
not be able to meet this double demand that is made upon it. 

It frequently happens that a break in compensation occurs 
even though the patient has taken great care not to exert him- 
self. Such a break in compensation may improve, and even 
be recovered from; but, on the other hand, it may lead to 
permanent insufficiency or death. The prognosis is decidedly 
better when the compensation of the right ventricle is alone 
at fault; and the breaks of compensation which occur in 
mitral disease are decidedly more favorable than those which 
develop in a heart in which the left or both ventricles are 
hypertrophied as a result of continued, severe exertion, arterio- 
sclerosis, or aortic valve disease. 

In a certain proportion of the cases in which such a break 
of compensation occurs, apparently spontaneously, it is to be 
attributed to a fresh infectious process involving the heart 
muscle. A second attack of acute articular rheumatism, a 
pneumonia, or a tonsillitis may in this manner be the imme- 
diate cause of a break in compensation. It seems as if the 
hypertrophied heart muscle formed a locus minoris resistentics 
to the infecting organisms or to their toxins. 

In another group of cases the apparently spontaneous break 
in compensation is due to the progressive character of the pro- 
cess that caused the hypertrophy. The demands upon the 
heart are gradually increased to such an extent that they cannot 
be carried out. Among such progressive processes are to be 
reckoned many valvular lesions, pulmonary cirrhosis and em- 
physema, arteriosclerosis, chronic nephritis, and the excessive 
use of beer; in a word, they include the majority of all the 
causes of heart hypertrophy. 



THE HEART 65 

Finally, the break may occur, not from any increase in the 
demands upon the hypertrophied heart, but from a progressive 
weakening of the muscle through myocardial disease, which 
renders the heart unable to do even its normal quota of work. 
This form of cardiac weakness will be more fully considered 
below. 

Causes of Primary Insufficiency of the Heart Muscle. — 
Some of the causes that lead to a primary weakness of the 
heart muscle have already been mentioned in the last section. 
The others may affect either hypertrophied or non-hypertro- 
phied hearts. 

Of first importance among these causes are those affections 
which interfere with the blood-supply to the cardiac muscle, 
such as thrombosis, embolism, and sclerosis of the coronary 
arteries. The heart is exceedingly sensitive to changes in its 
blood-supply. If a large portion of its wall be suddenly de- 
prived of its nourishment, the organ stops beating. This has 
been observed clinically when an embolus has lodged in a coro- 
nary artery, and it has been demonstrated experimentally by 
ligating one of these vessels. In other cases, where the damage 
is less extensive, the muscle wall may degenerate and rupture, 
leading to a fatal hemorrhage within the pericardial sac. 

The effect of occlusion of a branch of a coronary artery is 
variable. In some instances the patient experiences a sensa- 
tion of oppression or of severe pain in the precordium, which 
may or may not herald a fatal termination. Porter 07 has 
shown that it is possible to tie even large coronary branches 
without causing the death of the animal. Correspondingly, pa- 
tients have been observed at autopsy who have apparently re- 
covered from extensive infarctions of the heart muscle. There 
is a slight anastomosis among the branches of the coronary 
arteries, so that these can no longer be considered end-arteries 
in the strictest sense of the term. The anastomosis, however, is 

87 Jour, of Phys., vol. xv. p. 122. 

5 



66 CLINICAL PATHOLOGY 

insufficient to establish a collateral circulation if an area of 
any magnitude has been deprived of its regular blood-supply. 
An area so affected undergoes anaemic necrosis, and in general 
we may say that the occlusion of a coronary vessel of any 
magnitude is a matter of most serious import. 

Marked general anaemia also injures the heart, either by 
causing degeneration of its muscle-fibres or by lowering their 
nutrition in some other, less obvious manner. General bodily 
malnutrition exercises a similar unfavorable influence upon 
the strength of the cardiac muscle. It is comparatively unim- 
portant whether the malnutrition arise from poor food, gas- 
trointestinal disease, or infectious processes. In regard to in- 
fectious diseases, however, we must remember that they may 
injure the heart in a variety of other ways, as by causing myo- 
carditis, or through direct action of their toxins. The symp- 
toms which arise under these circumstances are irregularities 
of rhythm and, especially, those disturbances referable to a 
diminution in the heart's capacity for work. 68 

A fresh inflammation of the heart, whether of the endo- 
cardium, myocardium, or pericardium, is injurious to the 
heart's activities. In many cases there is an actual loss of 
contractile tissue as a result of the inflammation. As we have 
already mentioned, such changes not infrequently affect hearts 
which are already hypertrophied. They also occur, however, 
in previously normal hearts, especially from the general in- 
fectious diseases, such as acute articular rheumatism, diph- 
theria, typhoid fever, and scarlet fever. Such an infectious 
myocarditis may develop at the height of the disease, or it may 
not develop until some weeks after the fever has disappeared, 
as happens especially after scarlet and typhoid fevers. 

Numerous poisons may depress the activities of the heart, 
in some instances after a primary stimulation, as occurs with 
digitalis and muscarin. It is possible that similar poisons are 
88 Staehelin, Arch. f. klin. Med., vol. lxvii. p. 147. 



THE HEART 67 

generated in the metabolism of the body. We know of at 
least one disease in which the heart changes are probably due 
to such a cause, — viz., exophthalmic goitre. There is here an 
increase in the rate and in the force of the heart's contractions. 
In many cases an hypertrophy of both ventricles develops, and 
not a few of the patients die with the signs of a cardiac insuffi- 
ciency. At autopsy hypertrophy and dilatation of the heart are 
present, but no changes are found in the cardiac muscle. 69 
Since the blood-pressure in these cases is not always higher 
than normal, we must attribute the hypertrophy to the more 
rapid and forcible heart action, whether produced by nervous or 
by toxic influences. This illustrates the fact that hypertrophy 
may develop as a result of increased cardiac activity without 
there being any rise of blood-pressure. The bearing of such 
a possibility upon the causation of the hypertrophy associated 
with nephritis has already been considered (p. 51). Just as 
such toxic influences may increase the activities of the heart, 
so may they also lead finally to a weakening of the muscle. 

The toxins produced by bacteria may likewise injure the 
strength of the cardiac muscle. This has been proved beyond 
question in the case of the diphtheria toxins, and is probably 
equally true of others. 

It is difficult to say to what extent the so-called degenera- 
tions of the cardiac muscle injure the activities of the heart. 
Where the degenerations are very extensive, there can be no 
doubt that they cause serious disturbances. When, for exam- 
ple, in phosphorus poisoning, the ether extract amounts to 
twenty-six per cent, of the dried muscle instead of the normal 
eleven per cent., and when microscopic examination shows that 
nearly every fibre is filled with fat droplets, a diminished 
capacity for work is to be expected. We are not yet able, 
however, to estimate the effect of the slight and of the mod- 
erate grades of fatty or of hyaline degeneration. It is cus- 
■ Hczcl, Ztft. f. Nervcnhcilk., vol. iv. p. 353. 



68 CLINICAL PATHOLOGY 

tomary to attribute cardiac weakness to these conditions. Yet 
we know that the degenerations may be found in apparently 
strong as well as in weak hearts. 70 Furthermore, it is possible 
that the cause of the fatty degeneration may itself indepen- 
dently weaken the cardiac muscle. Brown atrophy has hardly 
any clinical significance, and we are not yet able to say what 
functional effect is produced by fragmentation of the cardiac 
muscle. 

The so-called fatty heart remains to be considered. This 
term has been applied to two separate conditions, — fatty de- 
generation of the muscle-fibres, and excessive fatty infiltration 
into the interstitial tissue. The two affections have nothing 
whatever to do with each other, and fatty degeneration rarely 
occurs to any marked degree in hearts which are the seat of 
fatty infiltration. The latter are usually associated with a 
general lipomatosis, and it is to them that the term " fatty 
heart" is more commonly applied. It is uncertain how much 
this excessive fat about the muscle-cells injures their functional 
activity. The muscular tissue is often surprisingly reduced 
in such hearts, probably from the pressure of the fat ; possibly, 
however, because the atrophy of the muscle is primary, the 
infiltration of the fat secondary. The disturbances of function 
in such hearts are probably due to the small amount of cardiac 
muscle present, relative to the total body weight. In other 
cases coronary sclerosis or other sequels of overindulgence 
in wine or beer constitute the cause of the cardiac weakness. 

Finally, there is a group of cases exhibiting weakness of 
the heart to which the term of " functional disturbances" has 
been applied. Such a term simply means that at present we are 
ignorant as to the cause of these disturbances. The number of 
cases included in this group will progressively diminish as 
our knowledge increases. At the present time we must place 
in this group many of those cases of hypertrophy in which 
70 Welch, Med. News, 1888. 



THE HEART 69 

the demands so increase that the heart is no longer able to 
meet them, as well as many cases of heart weakness resulting 
from disturbances of the general nutrition. Many of the so- 
called nervous derangements must likewise be placed in this 
group. 

Fatigue of the heart is just as little understood as is fatigue 
of the skeletal muscles. We speak of fatigue when the 
strength of a muscle diminishes as the result of exercise, and 
which is recovered after a period of rest. If the heart be 
diseased, it is fatigued by a smaller amount of work than is 
the normal organ, and not infrequently it recovers slowly or 
not at all. 

If sudden excessive demands be made upon a normal heart, 
it usually becomes fatigued, and after a rest it recovers. There 
have been cases described, however, in which a heart, as the 
result of a brief but excessive amount of work, was said to 
have been permanently injured, or, indeed, to have given 
out entirely. It has been considered that this resulted from 
an excessive dilatation of the heart. We know that such an 
acute dilatation with an arrest in diastole may be produced 
experimentally in animals by greatly increasing the resist- 
ance against which the heart must pump. The possibility 
that a similar result may occur in man from excessive ex- 
ertion cannot be denied absolutely. Yet the probabilities are 
entirely against this view. 71 In the reported cases of heart- 
failure following exertion, too little attention has been paid to 
the condition of the heart muscle, which has, in most instances, 
been previously damaged. 

There is no doubt that the diseased heart is not only easily 
fatigued, but that it is especially liable to become overdistended. 
When a convalescent from typhoid fever or diphtheria drops 
dead suddenly after some unusual exertion, it is usually from 
this cause. It is probable that fatigue or acute dilatation of a 

71 de la Camp. Zt ft. f. Win. Med., vol. li. p. I. 



70 CLINICAL PATHOLOGY 

slightly damaged heart frequently occurs without being recog- 
nized, and there always exists the danger that too much will 
be demanded of such a weakened heart. 

The influence of the nervous system upon the heart remains 
to be considered. It is theoretically possible that gross or 
microscopical lesions of the central nervous system should ex- 
ercise an unfavorable influence upon the heart's activities be- 
cause they injure the centres which regulate the heart, yet 
we have at present no direct evidence to prove that an injurious 
effect is actually produced by these causes. 

The central nervous system does in certain cases influence 
the heart unfavorably, but it is through the so-called psychic 
influences, which are of quite a different nature. It is well 
known that sorrow, worry, and care may affect the heart, not 
only in its rhythm, but in its strength. This is frequently ob- 
served in those suffering from heart disease, but it may occur 
also in healthy individuals. Indeed, the depression of the 
heart's activities may be so extreme as to terminate fatally. 72 
Neurasthenics frequently suffer from distressing cardiac sensa- 
tions, from irregularity of the heart's action, and even from 
cardiac weakness. This last, however, is not common, and it 
is more frequently a part of a general muscular weakness. 

Many are inclined to refer various disturbances of the 
heart's function to disease of the nervous mechanism situated 
within the heart itself, but we are without any exact knowl- 
edge on this subject. 

Cardiac weakness is ordinarily regarded as a weakness in 
the contractile power of the heart. Yet disturbances in the 
dilatation of the heart might almost equally well lead to serious 
consequences, 73 for diastole is not a merely passive process. 
There is probably an active dilatation at the beginning of 
diastole, and toward the end there is a rapid increase in the 

72 Bollinger, Munch, med. Wochenschr., 1888, No. 20. 

73 Romberg and Hasenfeld, Arch. f. exp. Path., vol. xxxix. p. 341. 



THE HEART 71 

tension of the muscular wall which limits the degree of filling 
of the ventricle. If these acts are improperly performed, 
serious alterations in the circulation would result, and possibly 
the effects of such disturbances will play an important part in 
the heart pathology of the future. At present, however, we 
are utterly ignorant of their practical significance. 

Results of Cardiac Weakness. — In the consideration of 
the effect of cardiac weakness upon the circulation, it is imma- 
terial whether the heart is primarily weakened so that it is 
unable to fulfil the ordinary demands of the circulation, or 
whether the demands are so increased that they become ex- 
cessive. 

Even the healthy ventricle does not expel the blood com- 
pletely when increased quantities must be pumped with each 
contraction. If the auricle weakens, it soon ceases to contract, 
especially if it be distended. This has been observed experi- 
mentally and clinically. 74 If the ventricle be weakened, it 
does not contract so completely as does the normal one, and 
a smaller amount of blood than usual is expelled at a lower 
rate of speed. The aorta is less completely filled and the 
arterial pressure sinks. The flow of blood into the ventricle is 
impeded, for not only is there less available space in the ven- 
tricle owing to the incomplete expulsion of blood, but the 
suction of early diastole is also probably weakened. Conse- 
quently the entrance of blood into the ventricle is impeded, 
the veins become distended, and the venous pressure increases. 

The effects are best studied in those cases in which both 
ventricles are equally or nearly equally affected, which is, in- 
deed, the commonest form of cardiac weakness. The insuffi- 
ciency of the left ventricle lowers the systemic arterial pressure, 
while the insufficiency of the right ventricle increases the 
pressure in the systemic veins. The difference in pressure be- 

74 D. Gerhardt, Arch. f. exp. Path., vol. xlvii. p. 250; Mackenzie, The 
Study of the Pulse, etc., 1902, chap. xx. 



72 CLINICAL PATHOLOGY 

tween the veins and arteries, therefore, is less than it is nor- 
mally, and consequently the rate of flow in the capillaries is 
lessened. At the same time, the distribution of blood is af- 
fected, for the arteries contain less, the veins more, blood than 
normal. Thus the result of a weakening of both ventricles 
upon the greater circulation is a diminished arterial pressure, 
an increased venous pressure, a diminution in the rate of blood- 
flow, and an overfilling of the veins with blood. Somewhat 
similar conditions result in the pulmonary circulation. 

If only one ventricle be weakened, or, as is more frequently 
the case, if one be decidedly weaker than the other, then the 
effects are quite different. Let us first consider the conse- 
quences of a weakened left ventricle. This leads to a lower 
pressure in the systemic arteries, and consequently to a slower 
rate of flow in the capillaries. The venous pressure in the 
pulmonary system is increased, and this leads to increased 
pressure in the pulmonary arteries, which necessitates more 
work for the right ventricle, as we have already explained 
(p. 43). Although the flow of blood through the lungs is 
maintained as well or nearly as well as before, yet the pul- 
monary vessels are overfilled, and this is not without its effect 
upon the interchange of gases in the lungs (p. 58). Further- 
more, these pulmonary changes react upon the general circu- 
lation, for the intrathoracic pressure is increased, and this 
lessens the aspiration of the blood from the great veins. In 
this manner an uncomplicated weakness of the left ventricle 
may cause stasis in the veins of the general circulation. In 
practice such a stasis is greatly favored by the fact that nearly 
every case of weakness of the left ventricle is associated with 
more or less weakness of the right. It may be asked whether 
or not it is possible for the right ventricle to pump its regular 
quota of blood if the left is only pumping a part of what it 
should. Such a condition would ultimately lead to an accu- 
mulation of all the blood of the body in the lungs. If life is 



THE HEART 73 

to be maintained, a stationary period must develop in which 
both ventricles pump equal amounts of blood. But during the 
time that it is developing, there is a gradual accumulation of 
blood in the lungs, so that in the fully developed condition 
there is an abnormal distribution of blood, more being in the 
lungs and less in the general circulation, even though both 
ventricles are now pumping equal amounts. 

If the right ventricle is insufficient, less blood is sent into 
the pulmonary arteries, the pulmonary pressure falls, and the 
rate of flow in the lungs is diminished. Less blood is taken 
from the great veins of the general circulation, these become 
swollen, and all the organs, especially the liver, become hyper- 
sonic from the venous congestion. The blood-flow in the gen- 
eral circulation is retarded, chiefly because the left ventricle 
cannot pump more blood than is furnished to it by the weak- 
ened right ventricle. 

As a matter of fact, cases in which one ventricle alone is 
weakened are extremely rare. Most injurious agents affect 
both sides of the heart. Diseases of the lungs, however, affect 
chiefly the right heart, while arteriosclerosis leads to disease of 
the left. In these conditions,- therefore, we are most likely to 
see pathological pictures corresponding to those just described 
as characteristic of weakness of only one ventricle. In all cases 
the blood-flow is retarded and there is labored breathing on 
account of the lessened amount of blood which traverses the 
lung in a unit of time. The disturbances of breathing are 
greater when the left ventricle is weakened, because this causes 
in addition a passive congestion of the lungs; whereas when 
insufficiency of the right heart exists alone, the blood tends to 
collect in the systemic veins without producing a pulmonary 
congestion. 

Of the harmful effects resulting from cardiac weakness, 
the most serious is unquestionably the slowing of the blood- 
current; next to this is the change in blood-pressure. We are 



74 CLINICAL PATHOLOGY 

accustomed to regard the latter as the more important, perhaps 
because estimations of the blood-pressure are made with com- 
parative ease. Yet in the last analysis the rate of blood-flow is 
of greater importance. This rate is, of course, largely de- 
pendent upon the arterial pressure, owing to the narrow range 
within which the venous pressure varies. (No deductions 
as to the rate of blood-flow can be made from the systolic 
arterial pressure alone, for with the same pressure the flow 
may vary enormously, depending upon the amount of resistance 
which it encounters in the smaller arterioles. The estimation 
of the difference between the systolic and diastolic arterial 
pressure promises to give us a rough method of estimating the 
flow of blood through the arteries. — Ed.) Nor can we say 
that the higher the arterial pressure the more favorable the 
condition, for a diminution of arterial pressure under certain 
conditions is of distinct advantage, and a great increase in 
pressure brings with it certain dangers. On the other hand, 
the lowering of pressure must not be excessive, for a certain 
arterial pressure is absolutely necessary to maintain the rate of 
blood-flow essential for the proper performance of the func- 
tions of the body. 

Disturbances of the heart's strength lead to its enlarge- 
ment through a dilatation of its cavities. The weakened 
ventricle, is unable to empty itself as completely as does the 
healthy one, and a certain amount of blood is left in it at the 
end of each systole. In diastole, likewise, it contains more 
blood than normal. There is, therefore, a dilatation of the 
ventricular cavity, and physical examination demonstrates an 
enlargement of the area of cardiac dulness. This dilatation 
of stasis must be sharply distinguished from the compensatory 
dilatation which we have already described in connection with 
certain valvular lesions. The latter are hardly pathological, 
for they are necessary in the accommodation of the heart to 
the new circulatory conditions. Only by such a compensatory 



THE HEART 75 

dilatation is the heart enabled to maintain a proper circulation 
in such valvular affections as aortic insufficiency (see p. 34). 
The dilatation which we are here considering is not of a com- 
pensatory nature, and it occurs only when the heart is unable 
to do its work. Although the normal heart does not empty 
itself completely when very large amounts of blood must be 
propelled, yet it soon regains its usual condition after the 
unusual demands have passed. In a case of pathological dila- 
tation, however, a complete systole never occurs, and the heart's 
cavities are constantly overfilled. 

This dilatation of a weakened heart may arise from many 
causes. A heart may be unable to maintain the circulation 
even when the body is at rest, in which case it is in a state of 
continual dilatation. On the other hand, the insufficiency may 
only develop when some extraordinary demands are made 
upon the heart, and in this case the dilatation is temporary. 
Hypertrophied hearts are especially susceptible to dilatation. 
They may maintain the circulation for years, in spite of the 
extra work necessary, but finally injurious influences weaken 
the muscle, or the work to be performed gradually increases 
beyond the capacity of the heart, and then dilatation follows. 
Frequently hypertrophy and dilatation develop together. This 
occurs when, at the same time, increased work is necessary and 
injurious influences act on the cardiac muscle. The ultimate 
outcome of such a case depends upon the relation between these 
two factors. If the hypertrophy be in excess, the prognosis 
is comparatively good, whereas if the dilatation be in excess 
it is comparatively bad. A dilated heart may gradually 
strengthen and hypertrophy, so that it will accommodate itself 
to the increased amount of work necessary. 

One effect of the poor circulation is a deficient supply of 
oxygen to, and an imperfect removal of carbon dioxide 
from, the tissues. The lessened blood-flow in the lungs also 
diminishes the interchange of gases there. The patient feels 



76 CLINICAL PATHOLOGY 

that he needs more air. The lack of oxygen and especially 
the presence of carbonic acid gas in the blood stimulate cer- 
tain cells of the medulla oblongata, and this stimulation causes 
more frequent and deeper respirations. (See Dyspnoea, in 
the chapter on Respiration.) The increase in respiratory 
movements may partly compensate for the slower blood-flow, 
but it does not do so wholly. 

The stasis of blood in the veins of the general circulation 
is very apparent. The superficial veins are enlarged and tor- 
tuous, and many, not before visible, appear. The poorly 
aerated blood gives a bluish tinge to the skin, which is usually 
most marked in the nose, ears, cheeks, fingers, and toes, prob- 
ably on account of relative coolness of these parts. 

The highest grade of cyanosis without a correspondingly 
great cardiac insufficiency is seen in congenital defects of the 
right heart. The fingers acquire a characteristic club-shape, 
owing to changes in the bones, and these, with the broad, 
dark-blue finger-nails, present a very characteristic appearance. 
It is difficult to give an adequate explanation of this cyanosis 
of congenital heart disease. A number of factors probably 
combine to bring it about. In the first place, owing to the in- 
ability of the right ventricle to completely compensate for the 
defect, there results an insufficient aeration of the blood and a 
stasis, the latter being evident from the tortuosity of the veins 
of the skin and of the backgrounds of the eyes. In the second 
place, a defect in the ventricular septum, so commonly asso- 
ciated with congenital lesions, allows the arterial and the 
venous blood to mix. Finally, the well-known increase in the 
number of red blood-corpuscles in a unit-volume is probably 
an important factor, which may account for certain cases of 
cyanosis that cannot be explained in any other manner. 

The venous hyperemia causes a swelling of distensible 
organs. The kidneys become enlarged and dark blue, and 
their secretion is altered in a characteristic manner. The liver 



THE HEART 77 

becomes swollen, hard, and tense, producing a distressing feel- 
ing of pressure. in the abdomen, or, indeed, actual pain. The 
plasma escapes from the capillaries into the subcutaneous tis- 
sues, causing oedema. Transudation into the serous cavities 
may also take place. 

If the veins are much swollen, they frequently pulsate 
synchronously with the heart-beats. These pulsations are most 
marked in the jugulars, but they may be present in the veins 
of the upper extremity or of the chest wall. 75 They are due, 
in the first place, to an insufficiency of the valves of the affected 
veins, which allows the pulsations normally present in the 
superior vena cava to be conducted to the peripheral veins. 
Such a " normal," " negative," venous pulse arises from a 
hinderance to the venous flow of blood caused by each con- 
traction of the right auricle. The vein is most distended during 
auricular systole just before the contraction of the ven- 
tricle. Tricuspid insufficiency produces a venous pulse of a 
totally different character. Here the vein is distended by the 
blood which regurgitates from the right ventricle through an 
insufficient tricuspid valve, and the greatest distention occurs 
synchronously with or just after the ventricular systole. This 
is called a " pathological," " positive" venous pulsation. With- 
out the aid of accurate tracings 76 it is often extremely difficult 
to determine which form of pulsation is present, owing to the 
irregular heart action and to the dyspnoea. 

Disturbances of the Heart-Rate. — Disturbances of the rate 
of the heart's beat may be due to a weakening of the heart or 
may be independent of such weakening. The heart-rate varies 
greatly even in health. It usually becomes slower with age, 
although in extreme old age it may again become more rapid. 
It is interesting to note that at this age the vagus tone is slight 

"D. Gerhardt, Arch. f. cxp. Path., vol. xxxiv. p. 402; Mackenzie, The 
Study of the Pulse, etc. 

7 ° See Mackenzie, loc. cit. 



78 CLINICAL PATHOLOGY 

or may be completely absent. 77 There are great individual 
variations in the heart-rate : while some have a normal rate 
of fifty-six to sixty-eight per minute, others have a pulse-rate 
of seventy to eighty. As a rule, the rate is more rapid in 
women than in men. It is not our intention to name all those 
influences which affect the rate of a normal heart. The mode 
of action of many is easily understood, whereas others have 
not yet been explained. 

Physiological studies 78 have demonstrated that the con- 
traction of the heart is initiated by a periodic stimulation of 
the fibres situated at the entrance of the great veins into the 
auricles. This stimulation is propagated from there over the 
whole heart, and causes its parts to contract in a regular 
sequence. The rhythm of a normal heart may seem absolutely 
regular to an ordinary observer, but more exact methods have 
shown that there are distinct physiological differences in the 
duration of the pulse-waves. According to Englemann, the 
heart's action may be affected in various ways. There may be 
variations not only in the regular sequence of the stimuli 
(chronotropy), but in the ability of the heart to respond to 
these stimuli (balmotropy). Furthermore, the propagation 
of the stimuli over the heart (dromotropy), as well as the 
contractility of the muscle (inotropy), may be abnormally in- 
creased or diminished. The causes of disturbances of cardiac 
rate and rhythm may lie either in the muscle itself or in its 
nervous connections. 79 Thus we see how complicated are the 
conditions governing the rate and rhythm of the heart, and 
how difficult it must be to interpret the many clinical variations. 

Rapid Heart Action (Tachycardia). — In certain conditions 
the cause of an abnormally rapid heart action is clear. For 

77 Dehio, Arch. f. klin. Med., vol. xli. p. 74. 

78 Gaskell, Jour, of Phys., vol. iv. p. 44; Engelmann, Pfliiger's Arch., 
vol. lxv. p. 535. 

79 Engelmann, Pfliiger's Arch. vol. lxv. pp. 109, 535. 



THE HEART 79 

example, atropine and similar drugs frequently increase the 
heart-rate by paralyzing the terminations of the pneumogastric 
nerve, although they can do this only in individuals in whom 
the vagus normally exerts an inhibitory action upon the heart. 
The same effect may be produced by pathological conditions 
of the vagus fibres or nuclei. Thus the rapid heart action 
which is so frequently observed at the end of meningeal in- 
flammations is due to a vagus paralysis following the period 
of vagus stimulation. Not infrequently a pulse-rate of ioo 
to 1 60 is observed in such cases without there being any other 
cardiovascular symptoms. 

It is more difficult to explain the rapid heart action due 
to exertion which is so frequently seen in convalescents, 
anaemic individuals, and in those who have heart disease. It is 
possible that there is here an increased irritability either of 
the heart itself or of its nervous connections, so that the chemi- 
cal products of muscular activity produce an unusual effect 
upon one or other of these tissues. 

Fever also causes a rapid heart action, for the increased 
temperature of the body stimulates both the central endings of 
the accelerator nerves and the heart muscle itself. If no 
other disturbing factors come into play, the rate of the heart 
increases proportionately to the rise in temperature. This 
parallelism between the temperature and the heart-rate is 
missed in certain infections. For example, in typhoid fever 
the pulse is relatively slow. With a temperature of 104 F. 
(40 C), we may have a pulse of seventy or eighty. In 
scarlet fever, on the other hand, the pulse-rate is usually sur- 
prisingly rapid. In these diseases the action of toxins prob- 
ably modifies the usual relation between the temperature and 
the pulse-rate. 

A diminution in the arterial pressure is usually accom- 
panied by an acceleration of the pulse. In many cases this is 
to be explained by the fact that there is a fall in cerebral 



80 CLINICAL PATHOLOGY 

pressure, which stimulates the central endings of the accelera- 
tor nerves. The purest example of this accelerating action is 
seen in the rapid pulse of widespread vasomotor paralysis 
(see p. 112). We frequently observe a rapid pulse in cases of 
cardiac weakness also, but in such cases it is uncertain whether 
the rapid heart action is attributable to the heart disease itself 
or to the fall in pressure. Experiments on animals would 
seem to indicate that an uncomplicated cardiac weakness leads 
to less frequent contractions, a fact favoring the hypothesis 
that the rapid action of the weakened heart is really due to 
the stimulation of the accelerator fibres occasioned by the 
lowering of the blood-pressure. 

In exophthalmic goitre the tachycardia may be continuous 
or it may occur in paroxysms. The symptoms of this disease 
are now attributed by many to an excessive thyroid metabolism, 
and it seems probable that the cardiac disturbances are like- 
wise due to this cause (see Chapter VII.). Heart symptoms 
of like nature may also develop in other diseases of the thy- 
roid gland. so We are ignorant as to which part of the cardiac 
mechanism is affected in these cases, whether it be the muscle, 
the cardiac ganglia, or the central nervous connections. 

The tachycardia of nervous people resembles that occurring 
in exophthalmic goitre. Even in healthy individuals an in- 
creased heart-rate may be induced by various influences, as 
exercise, psychic disturbances, and indigestion ; but in nervous 
people the response to these influences is excessive. It is pos- 
sible that the seat of the increased irritability is located in the 
cardiac muscle, for similar variations in rate are seen in those 
who suffer from disease of the myocardium, and in them at 
least there is no reason to assume that the condition is in any 
way dependent upon disturbances of the nervous system. 

A rapid heart-rate may be produced by disease of various 
other organs of the body, such as the peripheral nerves (espe- 
80 Minnich, Das Kropfherz, Leipzig, 1904. 



THE HEART 81 

daily of the left arm), the lungs, the liver, the genitals, and the 
gastro-intestinal canal. When the primary disease is cured, the 
cardiac disturbances disappear. Apparently such disturbances 
are due to reflexes from the diseased organs, a view which is 
supported by many facts. The patients are usually neurotic, 
the disturbances come and go in perplexing succession, and 
they furthermore usually arise from organs that are innervated 
by the vagus nerve. So far as the gastro-intestinal canal is 
concerned, the absorption of toxins might be the cause of the 
cardiac disturbances, but this explanation will not hold for the 
cardiac symptoms arising from disease in other organs. 

The condition known as paroxysmal tachycardia 81 is char- 
acterized by an enormously accelerated heart-rate, which be- 
gins suddenly, lasts a short time, and ceases as suddenly as it 
began. It may affect individuals with apparently normal 
hearts, or it may occur in those suffering from some definite 
cardiac disease. The duration of the attack may be minutes, 
hours, days, or even weeks. The pulse-rate usually ranges be- 
tween 150 and 300 per minute. The heart rhythm is regular 
and the sounds clear. The difference between the quality of 
the first and that of the second sounds tends to disappear, a 
common phenomenon in any great acceleration of the cardiac 
rate. The pulse is small. Ofttimes it cannot be counted. 
The blood-pressure is usually low, probably because the short- 
ness of diastole does not allow time for a complete filling of 
the ventricle. The patient may or may not suffer from dysp- 
noea. The jugular veins are always swollen and usually pul- 
sating. Other signs of venous stasis, such as swelling of the 
liver, albuminuria, and even oedema, may develop. 

Very often, even at the beginning of an attack, the heart 
is found to be enlarged, a noteworthy fact. Immediately 
after the attack it returns to its former size. Nevertheless, 
we have no right to consider this dilatation as the cause of 

81 A. Hoffman, Arch. f. klin. Med., vol. lxxviii. p. 39. 
6 



82 CLINICAL PATHOLOGY 

the paroxysm, for it has been found absent in some cases, by 
the most careful observers. 

An acute distention of the lungs has also been noted in 
certain cases, and the respiratory movements of the edges of 
the lungs have been diminished. To what extent these changes 
affect the heart is not definitely known. 

Subjective symptoms are always present. During the 
paroxysm nearly all patients feel weak and faint, most of them 
suffer from dyspnoea, and some experience the sense of im- 
pending death. As a rule, the symptoms begin and end sud- 
denly, frequently with peculiar sensations in the precordium; 
yet in some cases it is almost certain that the paroxysm may 
begin or end gradually. 

During the intervals between attacks the heart is often 
normal, so far as can be determined by physical examination. 
We should, however, be very cautious in our judgment of 
such cases, for it is difficult to exclude a coronary sclerosis, and 
many sufferers from this form of tachycardia are the subjects 
of easily recognized heart lesions. 

The individual attack may begin spontaneously, or it may 
be precipitated by some unusual exertion, by excitement, or 
by gastro-intestinal disturbances. These same causes normally 
lead to an acceleration of the heart's action, and it may be 
somewhat difficult to determine in the individual case whether 
the attack is really one of paroxysmal tachycardia or not. 

We are at present quite ignorant of the essential nature 
of this disease. It is impossible to produce such paroxysms 
of tachycardia, either in animals by vagus inhibition or in man 
by the administration of atropine ; yet many facts would seem 
to indicate that the disease is really of nervous origin, 82 chief 
among them the fact that, in many patients, pressure upon the 
vagus nerve will abort a paroxysm. 

(Hoffmann has made the important observation that the 
82 Rose, Berl. klin. Wochens., 1901, pp. 713, 744. 



THE HEART 83 

pulse-rate during the attack of paroxysmal tachycardia is pre- 
cisely double that immediately preceding or following the 
attack, 83 and some of Mackenzie's tracings support the same 
view. 84 These observations have given rise to the interesting 
hypothesis that normally the heart receives a greater number 
of stimuli than are responded to, and that the condition in 
paroxysmal tachycardia is merely one of an increased re- 
sponsiveness to these additional normal stimuli. — Ed.) 

The effect of an acceleration of the heart-rate upon the 
circulation is variable. It may lead in the first place to an in- 
creased blood-flow; but, on the other hand, the shortening of 
diastole may cause an insufficient filling of the ventricles with 
consequent retardation of the circulation. Thus experimental 
stimulation of the accelerator nerve produces more rapid and 
powerful cardiac contractions and an improvement of the cir- 
culation, whereas even the moderate acceleration caused by a 
vagus paralysis may lead to a slowing of the blood-current. 85 
A tachycardia may therefore affect the circulation of a patient 
in various ways, and numerous other factors must be con- 
sidered in the individual case. 

Slow Heart Action (Bradycardia). — A slow heart-rate may 
be due, in the first place, to a stimulation of the vagus nerve. 
We have an example of such a stimulation in the slow pulse of 
asphyxia. The venous blood stimulates the central endings of 
the pneumogastric nerve most powerfully. This tends in a 
certain degree to counteract the great rise in blood-pressure 
produced by the simultaneous constriction of the splanchnic 
vessels. 

The central terminations of the vagus nerve are likewise 
stimulated by any rise in the general arterial pressure. Slow- 
ing of the pulse is therefore always produced by such a rise, 

"Hoffmann, loc. cit, and Ztft. f. klin. Med., vol. liii. p. 206. 
M Mackenzie, The Study of the Pulse, etc., Figs. 91 and 107. 
"v. Basch, Phys. u. Path. d. Kreislaufes. 



84 CLINICAL PATHOLOGY 

unless other opposing factors are simultaneously operative. 
For example, the high blood-pressure due to acute nephritis 
nearly always causes a slowing of the pulse, and the slow pulse 
of digitalis is due in part to the same cause. If, however, the 
pressure rises gradually, and if it remains high for a long time, 
as happens in chronic nephritis and in some cases of arterio- 
sclerosis, then there is usually no reduction of the pulse-rate. 
The vagus endings probably become accustomed to the changed 
conditions, so that they no longer respond to the high arterial 
pressure. 

A rise in cerebral pressure will likewise stimulate the vagus, 
and we always find a slow pulse in those conditions which lead 
to rapid increase of pressure in the cranial cavity, such as intra- 
cranial hemorrhages and extensive meningitis. In such cases 
the vagus pulse is of great diagnostic significance. 

The vagus may be stimulated reflexly. The slow pulse ob- 
served at the onset of vomiting is caused by such a stimulation 
of the pneumogastric nerve, the blood-pressure being lowered 
at this time. This stimulation is usually due to a reflex from 
the stomach, although the vagus centre may be directly affected, 
as happens in the vomiting from increased cerebral pressure or 
from the action of such drugs as apomorphine. Clinically a 
reflex vagus pulse is frequently seen in the acute dyspepsia of 
children, in peritonitis, in strangulation of the intestines, and 
in chronic constipation. In such conditions the stimulation may 
produce not only a slow, but an. irregular heart action. 

Bradycardia may be produced by the direct action of certain 
poisons, as, for example, muscarin and the bile salts. 86 In the 
early stages of catarrhal jaundice, there is always a slowing of 
the heart-rate, and often irregularities of rhythm. In the 
chronic jaundice accompanying diseases of the liver itself, and 
in those associated with infectious diseases, the bradycardia is 

88 Weintraud, Arch. f. exp. Path., vol. xxxiv. p. 2,7 \ Brandenburg, 
Berl. klin. Wochensch., 1903, No. 38; Suppl., p. 149. 



THE HEART 85 

often absent, probably because smaller amounts of bile salts are 
manufactured or because other factors influence the heart. 
Even in the marked jaundice of chronic obstruction of the 
common duct by stone or by tumor there is frequently no slow- 
ing of the pulse. This is probably due to a diminished pro- 
duction of the bile salts, although possibly the body becomes 
accustomed to their presence. Experimental investigations 
have shown that the bile salts act both upon the central and the 
peripheral terminations of the vagus nerve, as well as upon the 
cardiac muscle itself. In catarrhal icterus, we cannot say at 
present which action is the most important in the production 
of the typical slow pulse. The hypothetical ursemic poison 
likewise slows the heart-rate, but we are ignorant of the manner 
in which it acts. 

In all cases of continued vagus irritation the slowing of 
the pulse is only of moderate grade, rarely going below 44 to 
48 per minute. The irregular pulse so frequently observed 
in these conditions well corresponds with the results of experi- 
mental stimulation of the vagus nerve. 

All varieties of bradycardia, other than those caused by 
vagus stimulation, are difficult to explain. A slow pulse may 
be present in neurotic individuals, but we are unable to say 
whether the immediate cause lies in some alteration in the 
nervous system, or in some changes in the heart muscle. 

There is a group of bradycardias caused by changes in the 
heart itself. An increase in intracardiac pressure will cause a 
slowing of the heart-rate, as may be observed in cases of aortic 
stenosis and also, in certain instances, as a result of unusual, 
excessive exertion. In such cases the bradycardia is advan- 
tageous, for it tends to lessen the work of the heart. 

The bradycardias which follow infectious diseases are like- 
wise due to changes in the heart. They may be likened to the 
subnormal temperature which is so frequently present under 
like conditions. The slowing of the pulse is most marked after 



86 CLINICAL PATHOLOGY 

pneumonia and typhoid fever. The injection of atropine does 
not affect the bradycardias of this origin. 87 Since atropine 
paralyzes the vagus terminals, and since the paralysis of these 
terminals does not affect the bradycardias under consideration, 
it must be inferred that they are due to changes in the cardiac 
muscle. Many would attribute this slowing of the heart to 
fatigue of the muscle. Yet we know that fatigue is not usually 
associated with a slow pulse. Furthermore, it has not been 
shown that all infectious diseases necessitate increased work for 
the heart, which is especially true of typhoid fever with its 
relatively slow heart-rate. It seems more probable, therefore, 
that the post-febrile bradycardia is really an expression of 
cardiac weakness. This is not synonymous with fatigue, for 
the latter presupposes a previous period of exertion. We 
know that the weakened heart not infrequently contracts at a 
slower rate than normal. We also know that other signs of 
weakness are frequently present during convalescence, and that 
a cardiac insufficiency is especially prone to develop at this time. 

The bradycardias which appear at the height of infec- 
tious diseases, especially that ominous slowing of the pulse 
during the course of diphtheria, are doubtless to be referred to 
changes in the cardiac muscle itself. Before they can be ac- 
curately classified, however, it will be necessary to determine 
their exact relation to the various degenerations in the heart 
muscle which occur in these diseases. 

Anatomical changes in the myocardium may lead to a 
slowing of the pulse. This is seen in both acute and chronic 
myocarditis, as well as in the changes which follow diseases 
of the coronary arteries. The pulse may fall to twelve a minute 
in these conditions, and a slow pulse may persist for years. A 
slow pulse is furthermore observed occasionally in very stout 
individuals, and in those who have devoted themselves over- 
zealously to the pleasures of the table, of wine, and of tobacco. 

87 Dehio, Arch. f. klin. Med., vol. Hi. p. 74. 



THE HEART 87 

We are inclined to attribute the bradycardia in such individuals 
to an associated coronary disease. 

Observations on the venous pulse have demonstrated that 
in certain cases of slow arterial pulse the auricles are con- 
tracting more rapidly than are the ventricles. This is seen 
most frequently in that paroxysmal type of bradycardia known 
as the Adams-Stokes disease. 88 To explain the difference in 
rate between the ventricles and the auricles, we may assume 
that some of the waves of contraction, which normally proceed 
from the auricles to the ventricles, are blocked at the auriculo- 
ventricular ring so that the ventricles contract less frequently 
than do the auricles, thus giving rise to the so-called blocked 
heart. 

The bradycardia of the puerperium is probably due to the 
decrease in the work of the heart which follows the delivery 
of the child. 

We have already mentioned some of the effects of a slow 
heart action upon the circulation. The heart is enabled to 
recover itself during the lengthened diastolic pause, and its 
work is, to a certain extent, diminished. The velocity of the 
blood-current is lessened, yet this may be very slight if the 
slowing of the heart is only moderate in degree. If the brady- 
cardia be due to vagus irritation, the individual contractions 
are not only less frequent but they are less forcible, and the 
current may be slowed considerably. Whenever the brady- 
cardia is extreme, the velocity of the blood-stream and the 
arterial pressure are always markedly diminished. Such pa- 
tients cannot exert themselves without dyspnoea, and even when 
at rest they may suffer from syncopal attacks. 

Disturbances of Cardiac Rhythm (Arrhythmia). — Our 
knowledge of the disturbances of the rhythm of the heart is 
naturally limited by our knowledge of the origin and nature of 

"His, Arch. f. klin. Med., vol. lxiv. p. 316; Osier, Lancet, August 22, 
1903. 



88 



CLINICAL PATHOLOGY 



the normal cardiac rhythm (see p. 78 ). 89 The pulse is not an 
absolute guide to the rhythm of the heart ; first, because a very 
weak contraction of the heart may not give rise to an arterial 
pulse; and secondly, because waves of different size may be 
propagated at different rates of speed toward the periphery. 
Thus the rhythm at the wrist may differ considerably from that 
at the heart. 

Forms of Arrhythmia. — (Physiological studies have shown 
that the heart may be made to contract prematurely if an 
" extra stimulus" be applied, either to a ventricle or to an 

Fig. 1. 




The upper tracing was drawn by the ventricle, the middle by the auricle, and the lower 
by a sphygmograph attached to the carotid artery. During the systoles of the ventricles and 
auricles the levers made downward strokes, during diastoles upward strokes. The ventricle 
was stimulated at x. (From Cushny, Jour, of Exp. Med., vol. iv. p. 329.) 

auricle. Such a contraction is called an extrasystole. Thus 
in Fig. 1, in which the upper tracing represents the contractions 
of the ventricle, the middle those of the auricle, and the lower 
the pulse, the ventricle received an electrical stimulus at the 
point x. It will be seen that this resulted in the premature 

69 Engelmann, Pfliiger's Arch., vol. lxii. p. 543 ; Hering, Pfliiger's Arch., 
vol. lxxxii. p. 1 ; Ebstein, Arch. f. klin. Med., vol. lxv. p. 81 ; J. Mackenzie, 
The Study of the Pulse, etc. 



THE HEART 



89 



ventricular extrasystole, c' , whereas the auricular rhythm re- 
mained regular. The stimulus proceeding from the auricular 
contraction, C, found the ventricle in the refractory period just 
following its extrasystole c' , and consequently it was without 
effect and this contraction was omitted. The ventricle did not 
again contract until the stimulus from the auricular contrac- 
tion D reached it, causing the ventricular contraction d. Since 
the auricle had maintained its regular rhythm during the extra 
ventricular contraction, the premature extrasystole, c' , is fol- 
lowed by a correspondingly long pause, and the time from b to 
d is exactlv twice that between normal beats. If, as in Fig 2, 



Fig. 2. 




The upper tracing was drawn by the ventricle, the middle by the auricle, and the lower 
by a Bphygmograph attached to the carotid artery. During the systoles of the ventricles and 
auricles the levers made downward strokes, during diastoles upward strokes. The auricle 
was stimulated at about the point x. (From Cushny, loc. cit.) 



the extra stimulus be applied to the auricle, it is Eollowed by an 
extra contraction, not only of the auricle C, but of the ventricle 
c'. In this instance the auricular rhythm is disturbed, and 
although there is a compensatory pause after the extra auricu- 
lar systole, it is not usually long enough to make the total b 
to d equal to twice the interval between normal beats. — Ed.) 



90 



CLINICAL PATHOLOGY 



The occurrence of extrasystoles in man seems to be favored 
by a high arterial pressure and by myocardial disease. The 
premature contraction may occur at varying periods after the 
normal contraction. The resulting extra pulse is weaker than 
the normal one, partly because the shortness of the preceding 
diastole does not allow sufficient time for the ventricle to 
become completely rilled with blood, and partly because the 
extra stimulus affects the ventricle while it is still in a some- 
what refractory stage just following the normal contraction. 
It is, therefore, a general rule that the earlier the extrasystole 
occurs after the normal contraction, the smaller will be the 
resulting pulse. Indeed, the extrasystole may not produce a 
pulse at all, in which case there is an intermission in the 
regular pulse rhythm. (See Fig. i.) 

The extrasystole is almost invariably followed by a com- 
pensatory pause, owing to the omission of the regular contrac- 

Fig. 3. 




Simultaneous tracings of the apex-beat (contractions of the left ventricle) and of the 
jugular pulse (contractions of the right auricle). The indentations, marked p on the latter, 
are due to the transmitted carotid pulse. It will be noticed that whereas the auricle contracts 
regularly, the rhythm of the ventricle is interrupted by a number of extrasystoles, b' , e' , h' , 
etc., and the interval between the normal contractions preceding and following such extra- 
systoles, as d to/, is approximately double that between normal beats, as f to g. (From 
Mackenzie.) 



tion, that was due immediately after the extra contraction. 
The time, therefore, between the normal beats preceding and 
following the extrasystole is approximately twice the normal 
period between regular beats. We have taken pains to show 
that when the extra stimulus is experimentally applied to the 
ventricle, this doubling of the time between normal beats is 



THE HEART 



91 



very exact owing to the unimpaired rhythm of the auricles. 
It has also been shown clinically that the auricles do not neces- 
sarily participate in the irregular action of the ventricles 
(see Fig. 3). If the extra stimulus affects the auricles, then 
they participate in the irregularities of the ventricles (see 
Fig. 4) . In such a case the interval between the normal beats 
preceding and following the extrasystole may equal two normal 
intervals, or it may be less than this. If the stimulus be ap- 
plied to the mouths of the great veins, then the interval is 
always less than two normal intervals. 

Those extrasystoles which are caused by increased arterial 
pressure usually involve the ventricles alone, whereas those 
due to myocardial disease may begin either in the auricles or 

ventricles. 

Fig. 4. 




artery. 



Simultaneous tracings of the radial artery (contractions of the left ventricle) and of the right 
jugular vein (contractions of the right auricle). It will be noticed (i) that the auricle here partakes 
in the irregularity, V ; and (2) that the interval between A and C is less than twice that between C 
and D. (From Mackenzie). 

(Extrasystoles occur singly or in various combinations. 
Thus a normal beat may be regularly followed by an extra- 
systole, producing the well-known bigeminal rhythm. (See 
Fig. 5.) On the other hand, the extra contraction may follow 
every second, or every third beat, etc., or a series of extra- 
systoles may follow one another. In this manner various 
forms of arrhythmia may be produced by the occurrence of 
extrasystoles alone. — Ed.) 

Arrhythmias may be due not to extrasystoles, but to dis- 
turbances in the normal automatic stimuli to the auricles. 
These have been termed "true arrhythmias." 90 The subject 

80 Wenckebach, Ztft. f. klin. Med., vol. xxxvi. p. 181 ; vol. xxxvii. p. 
475 ; vol. xxxix. p. 293. 



92 



CLINICAL PATHOLOGY 



is, however, still so new that it is hardly permissible for us to 
draw important diagnostic and prognostic conclusions from 
the character of the arrhythmia. 















Fig 


5- 










i\ 


[\ 


t\ 


h 


> 


\ 


\ 


\ 


\ 


\ 


\ 


NJ 



ii O >-> 



A pulsus trigeminus with the transition to a regular pulse. Notice that the double interval of 
the former (6.8 fifths of a second) is less than twice the period of a single interval of the latter 
(2 X 3.75 = 7.5), from which fact we may infer that the extrasystoles were probably of auricular 
origin. 



In those cases in which only every other systole gives rise 
to an arterial pulse, the possibility exists that the condition is 
caused by a " hemisystole;" i.e., by the alternate independent 
contractions of the right and left ventricles. Although this 
condition of hemisystole has been observed experimentally, we 
have no proof that it actually occurs in man. Indeed, most 
of the cases which have been carefully investigated have been 
shown to be instances of bigeminal rhythm, due to extrasystoles 
in which only every other contraction gives rise to an arterial 
pulse. 91 (Some of Mackenzie's tracings (Chapter XXIX.) 
from dying hearts admit of hardly any other interpretation 
than that of a non-simultaneous contraction of the two ven- 
tricles. — Ed.) 

The injured heart of an animal may beat at regular inter- 
vals, but with alternating strong and weak contractions. Such 
a " pulsus alternans" is very uncommon clinically, and some 
claim, indeed, that all cases so reported are in reality instances 
of bigeminal rhythm due to the occurrence of regular extra- 

01 Riegel, Deut. med. Wochens., 1903, No. 44; Hering, ibid., No. 22. 



THE HEART 93 

systoles, although others maintain that a true " pulsus alter- 
nans" may occur in man. 92 

Causes of Arrhythmia. — Disturbances of the cardiac 
rhythm frequently result from disease of the myocardium. In- 
flammatory processes and infarcts resulting from coronary dis- 
ease are more frequently the causes of such arrhythmias than 
are the parenchymatous degenerations of the muscle. A dimin- 
ished supply of blood to the heart, due to a narrowing of the 
coronary arteries, may also lead to irregularity. Myocarditis 
and coronary sclerosis are therefore to be regarded as the 
most frequent causes of cardiac arrhythmia, and they are 
doubtless responsible for many of those disturbances of rhythm 
which occur in the aged. Yet there seems to be no strict rela- 
tion between the extent of the disease and the degree of irregu- 
larity. Possibly the location of the disease is of paramount 
importance, and it is, indeed, claimed that disease of the 
auricular musculature is especially liable to lead to irregulari- 
ties in rhythm. The musculature at the mouths of the great 
veins, where the contraction wave starts, should be especially 
examined in all cases of irregular heart action. 

Cardiac arrhythmia may occur without any demonstrable 
anatomical changes in the myocardium. The irregular pulse, 
which so frequently develops at the height of or during the 
convalescence from 'the acute infectious diseases, is probably 
due to a weakness of the heart, and, as has been mentioned, 
it is often associated with a bradycardia (p. 85). In many 
instances this irregularity is only an exaggeration of the 
slight variations in rate which normally accompany respira- 
tion. 9 ' 5 

An irregular pulse may result from vagus stimulation, for 
such a stimulation not only slows the heart-rate, but often 
produces irregularities in rhythm. 

K Hoffman, loc. cit. 

"LomiiK'l, Arch. f. klin. Med., vol. Ixxii. p. 465. 



94 CLINICAL PATHOLOGY 

appear if the influence of the vagus upon the heart be eliminated 
by the administration of atropine. 

We are quite ignorant as to the nature of the arrhythmia 
which is observed in the so-called cardiac neuroses, resulting 
from neurasthenia, masturbation, excitement, etc. In such 
cases, the heart may beat first slowly, then rapidly, the indi- 
vidual beats may follow each other quite irregularly, or finally 
the normal respiratory variations may be excessively exag- 
gerated. 94 

Reflexes may give rise to irregularities of the heart's 
action. We know that if the endocardium be touched during 
the course of an experiment, irregularity results. How im- 
portant a part such reflexes play in clinical pathology is uncer- 
tain. Possibly the arrhythmia of endocarditis may arise from 
such reflexes; possibly the arrhythmias sometimes seen in 
gastro-intestinal diseases are also of reflex nature. In both 
these examples, however, there are usually other factors present 
which might produce an irregular heart action. 

Arrhythmia may be due to the action of poisons, notably 
of digitalis, caffeine, tobacco, and the toxins of uraemia. The 
irregular tobacco heart is well known. The toxins of infectious 
diseases, especially those of typhoid fever and diphtheria, may 
produce similar effects. 

In chronic pericarditis and mediastinitis it is possible for 
the new-formed connective tissue to compress the aorta or the 
great veins during inspiration. This would lead to a diminu- 
tion or disappearance of the pulse during inspiration (pulsus 
paradoxus). Not every pulsus paradoxus is capable of being 
explained in this manner. It has been observed in simple 
insufficiency of the heart, and especially in association with 
stenosis of the larger air-passages, and under such circum- 
stances the cause must lie in the heart itself. 95 

94 Lommel, Arch. f. klin. Med., vol. lxxii. p. 465. 
* 5 Riegel, Deut. med. Wochens., 1903, No. 20. 



THE HEART 95 

The Cardiac Impulse — If we inspect the chest of a normal 
individual, a periodic heaving is usually seen in the fifth inter- 
costal space, median to the mammary line. This is called the 
cardiac impulse. It is produced normally by the apex of the 
left ventricle, which is thrust into the intercostal space with 
each systole. During diastole, the heart is flaccid and tends 
to assume the shape given to it by its surroundings, but in 
systole it becomes rigid and assumes its own characteristic 
shape. This throws the apex against the chest wall, and is 
the principal factor in producing the impulse. The main part 
of the impulse occurs during the first period of systole at a 
time when all the valves are closed. The heave, however, con- 
tinues a short time after the opening of the aortic semilunar 
valves. 

Many factors may therefore affect the cardiac impulse, 
such as the position of the apex within the chest cavity, the 
force with which the heart contracts, and the condition of the 
chest wall and the overlying border of the left lung. Provided 
the latter do not play too great a part, we may say in general 
that a powerful systole will produce a strong, heaving impulse, 
and a weak systole will give rise to a small and soft impulse. 
It cannot be assumed, however, that an extensive, strong im- 
pulse is always due to a more powerful contraction of the 
heart muscle. If an hypertrophy of the right ventricle is 
mainly responsible for the condition of cardiac hypertrophy, 
as frequently happens in mitral stenosis, then the apex of the 
heart is usually formed by the right ventricle. 

Long-continued hypertrophy of the heart may lead to a 
bulging of the chest wall, which is most marked if the enlarge- 
ment of the heart occurred at a time when the bones of the 
thorax were soft, and consequently it is most often seen in 
young individuals. 

Attempts to draw deductions from the shape of the graphic 
representations of the cardiac impulse have proved of little 



96 CLINICAL PATHOLOGY 

clinical value. (Mackenzie 90 claims that if the apex of the 
heart is formed by the right ventricle, there is a systolic 
retraction in the apical region instead of the normal impulse. 
It is certain also that tracings of the cardiac impulse may 
show ventricular contractions which do not influence the radial 
pulse. — Ed.) 

The Heart-Sounds. — The heart-sounds may be altered 
in either their intensity or their character. One of the most 
important of these alterations is the increase in the loudness 
of either the pulmonic or the aortic second sound. This 
accentuation is generally indicative of an abnormally high 
pressure in the corresponding artery. Since the pressure in 
the aorta is normally more than twice as great as that in the 
pulmonary artery, one might think that the aortic second sound 
would be normally much louder than the pulmonic second 
sound. Such is not the case, however. Examination of healthy 
individuals shows that there is but little difference between 
the second sounds in either intensity or character. As a rule, 
the pulmonic second sound is relatively somewhat louder in 
childhood, but with advancing years the relation gradually 
changes until in old age the aortic sound is usually the 
louder. 97 The deep position of the aortic valves is hardly an 
adequate explanation for the relative weakness of the aortic 
second sound, and indeed no good explanation for it is known. 

We have said that, in general, an accentuation of a second 
sound indicates an increase of pressure in the corresponding 
artery. Yet we meet cases in which increased pressure is 
present without an accentuation of the corresponding sound, 
and, conversely, accentuation of the second sound may be pres- 
ent without there being any increase of pressure. Other factors 
must come into play. Of these the proximity of the vessels 

93 Loc. cit. 

07 Vierordt, Die Messung der Intensitat der Herztone, Tubingen, 1885 ; 
Cabot, Physical Diag., p. 123. 



THE HEART 97 

to the chest wall is unquestionably of importance. The wall 
of the artery also probably influences the sound produced, and 
not infrequently we observe a loud, ringing aortic second sound 
in arteriosclerosis of the first part of the aorta, even though 
there is no increase of blood-pressure. 

Accentuation of the second pulmonic sound is caused by 
conditions which lead to an increase of pressure in the pul- 
monary circulation. These conditions, which have already 
been enumerated (see p. 43), include mitral disease, weak- 
ness of the left ventricle, pulmonary emphysema, etc. The 
accentuation is ordinarily associated with an hypertrophy of 
the right ventricle, for both are caused by the increased press- 
ure in the pulmonary artery. 

Acute and chronic nephritides usually cause accentuation 
of the second aortic sound, and in many cases an accentuation 
of the second pulmonic as well. It will be recalled that 
this latter class of cases furnished part of the evidence which 
led us to assume that both ventricles do increased work in 
nephritis. In these renal diseases, the aortic second sound 
is not only louder than normal, but it frequently possesses a 
peculiar ringing quality, which is probably clue to changes 
in the wall of the aorta. 

Accentuation of the first sound is present in many cases 
of mitral stenosis, in which disease it may indeed be audible 
at some distance from the chest wall. The most acceptable 
explanation of this accentuated first sound is that it is due to 
a more rapid systole of the left ventricle, occasioned by the 
abnormally small amount of blood which this receives during 
diastole. This explanation receives support from the follow- 
ing facts. In the first place, when the right heart weakens 
and when correspondingly less blood is sent to the left ven- 
tricle, the accentuation of the first sound frequently becomes 
more marked. In the second place, a loud first sound is fre- 
quently heard after severe hemorrhage, and in this condition 

7 



98 CLINICAL PATHOLOGY 

it is almost certain that the accentuation is due to a shortened, 
rapid systole. 

The first sound is usually loud when the heart is beating 
rapidly. Here, again, the ventricle is incompletely filled and 
the contraction is rapid. Quincke 98 has described abortive 
contractions of the heart which follow immediately upon 
normal ones in which a good filling of the ventricle was an 
impossibility and in which the systole was short. In these 
the first sound was often, but not always, louder than normal. 
The powerful contraction of an hypertrophied heart rarely 
produces a loud first sound, but usually an impure and muf- 
fled one. Weak and anaemic individuals, on the other hand, 
frequently show surprisingly loud first heart-sounds. 

In certain cases, a doubling of one or other of the heart- 
sounds is heard, so that three sounds may be distinguished 
instead of two. This is most frequently due to a reduplica- 
tion of the second sounds, which may sometimes be heard 
even in healthy individuals, more especially at the height of 
inspiration. It may also be present in various heart diseases, 
notably in affections of the mitral valves. This reduplication 
of the second sound is caused by a non-simultaneous closure 
of the two sets of semilunar valves. It may be conceived that 
the difference in the time of closure is due to an unequal 
duration of the right and left ventricular systoles, because 
one ventricle must do more work than the other. Such an 
explanation accounts very well for the reduplication of mitral 
valve disease. Why it should occur in normal individuals, 
and why it should be absent in cases where we have reason 
to believe that the systole of one side is lengthened, are not 
so readily understood. 

A doubling of the second sound is frequently heard at the 
apex in cases of mitral stenosis. In this case the pause between 
the two second sounds is longer than it usually is between 

88 Arch. f. klin. Med., vol. liii. p. 414. 



THE HEART 99 

reduplicated sounds. Possibly the extra tone is in reality a 
rudimentary murmur, or possibly it is produced by the auricu- 
lar contraction. 

Reduplication of the first sound is less common than 
reduplication of the second. In place of a single first sound, 
we hear two, the second being, as a rule, the louder. This is 
considered ordinarily to be due to a non-simultaneous con- 
traction of the two ventricles, but it must be admitted that 
the explanation is not beyond question. 

In gallop rhythm we likewise hear three heart-sounds in- 
stead of two, the extra sound being heard shortly before the 
usual first sound. As a rule, this extra sound is comparatively- 
faint and muffled, and is distinctly separated from the first sound 
following it. This form of gallop rhythm is most frequently 
observed when an hypertrophied heart weakens, and above all 
when the hypertrophy is caused by chronic nephritis. Gallop 
rhythm may, however, result from arteriosclerosis, from myo- 
carditis, and from the acute infectious diseases, and may even be 
present in apparently healthy hearts. It is quite probable that 
the extra heart-sound is produced by the contraction of the 
auricle. We know that the auricular contraction does produce 
a tone, but that in health this so immediately precedes the 
ventricular sound that it is merged into it and only one sound 
is heard for both contractions. If a pause intervene between 
the two contractions, then we could hear two sounds, and 
possibly such is the case in gallop rhythm." 

The quality or character of the first sound may change, but 
unfortunately the cause and the meaning of such changes 
are but little understood. A muffled or " impure" sound may 
be heard without there being any anatomical changes present 
in the valves ; but, on the other hand, such an " impure" 
sound may herald the onset of a valvular lesion. Many such 
changes are possibly caused by some variation in the manner 
" Krcige and Schmall, Ztft. f. klin. Med., vol. xviii. p. 261. 



100 CLINICAL PATHOLOGY 

of the muscular contraction, others by changes in the tension 
of the valves, but as yet we cannot accurately interpret the 
meaning of the muffled, impure first sound. 

The first sound may be fainter than normal, even though 
the ventricle is contracting powerfully; yet, on the other 
hand, a faint first sound may be due to a weakening of the 
ventricular contraction. I have observed a disappearance of 
the first sound in a case of typhoid fever in which at autopsy 
no macroscopical changes were found in the heart. In syn- 
cope the heart sounds are often extremely faint, and since 
the pulse is also very weak, we must assume that in this 
condition a weak heart action is responsible for the faintness 
of the cardiac sounds. 

Cardiac Murmurs. — If the auriculo- ventricular valves 
allow the blood to flow back into the auricles during systole, 
eddies are produced by the mingling of this stream of blood 
with the one coming in from the great veins. These eddies 
set the valves in vibration very much as the violinist's bow 
causes the strings of the violin to tremble. Such vibrations 
of the valves give rise to the abnormal heart-sounds known 
as murmurs. In the case just described, the murmur is pro- 
duced during the systole of the ventricle, and we speak of it 
as a systolic murmur. Such a murmur assists us in diag- 
nosticating a leakage backward through the auriculo-ventricu- 
lar opening. 

If the semilunar valves are insufficient, either because they 
are shrunken or because the orifice is dilated, then the murmur 
is produced in diastole, at which period the blood streams from 
the aorta back into the ventricle and there causes the eddies 
which set the valves in vibration. The murmur may be heard 
throughout diastole, or it may be present only in the earlier 
part, at which time the negative pressure caused by the active 
dilatation of the ventricle most favors a leak backward from 
the aorta. 



THE HEART 101 

An obstruction to the flow of blood through any of the 
orifices of the heart 'may produce a murmur, and a simple 
roughening of the valves at the aortic orifice may do the same. 
The murmur caused by a stenosis of the mitral or of the 
tricuspid orifices is heard during a part or the whole of the 
diastole of the ventricles. When it persists throughout this 
period it is usually loudest at the onset and at the termination. 
The former accentuation is caused by the suction of the 
dilating ventricle; the latter by the auricular contraction. 
More frequently these murmurs are only heard during a part 
of the diastole, either at the beginning or at the end. The 
latter, called a presystolic murmur, precedes and runs up into 
the first heart-sound, and is especially characteristic of the 
lesion of mitral stenosis. 

The murmurs produced by a narrowing or roughening of 
the semilunar valves are usually loud and rough. They occur 
at the time that the blood is passing from the ventricles into 
the great arterial trunks. It is sometimes possible to demon- 
strate that they begin somewhat later than the beginning of 
the cardiac impulse, for it must be remembered that the first 
part of this impulse corresponds to that period of the ven- 
tricular contraction during which the intraventricular pressure 
is being raised to the level of pressure which exists in the 
great arterial trunks. For this reason no blood is leaving 
the ventricles during the first portion of the cardiac impulse, 
and consequently no murmur due to an obstruction at the 
aortic orifice can be produced at that time. 

In many cases of mitral insufficiency the first sound is well 
heard. It may be even louder than normal, especially if an 
associated mitral stenosis be present. Frequently, however, 
the first sound is not heard at the point of maximum cardiac 
impulse. In some such cases we may assume that the normal 
sound is overshadowed by the loudness of the murmur, but 
in others it seems to be absent for some other, unknown reason. 



102 CLINICAL PATHOLOGY 

In aortic stenosis the first sound may also disappear, not only- 
over the aortic area, but at the apex as well. The left ven- 
tricle appears to contract without producing an audible first 
sound. This is possibly due to the gradual and prolonged 
systole which is so characteristic of aortic stenosis. In aortic 
regurgitation the second sound may become very faint or it 
may disappear entirely. 

Various opinions are held as to the cause of those mur- 
murs, which have been variously designated as accidental, 
functional, or haemic murmurs. They are usually systolic in 
time, and are most intense in the second intercostal space 
to the left of the sternum and at the point of maximum 
cardiac impulse. It is quite certain that they are not due to an 
endocarditis affecting the mitral valves. We cannot exclude 
with equal certainty, however, the presence of functional in- 
sufficiencies of the auriculo-ventricular orifice. Indeed, it 
appears to me that this is the cause of many of these murmurs. 
They are heard most frequently in weak and anaemic indi- 
viduals, such as would be most liable to have a weak cardiac 
muscle, dilatation of the cavities of the heart, and functional 
insufficiency of the mitral and tricuspid orifices. The second 
pulmonic sound is frequently found to be accentuated, which 
would also favor the idea that there is some damming back in 
the pulmonary circulation. It seems improbable that all func- 
tional murmurs are produced in the manner described, for 
many are not accompanied by an accentuation of the second 
pulmonic sound. 

Diastolic functional murmurs, which simulate the murmur 
of aortic insufficiency, are very uncommon. Most of these 
are probably produced in the great veins, and are simply 
transmitted to the precordium. 100 Some, however, cannot be 
thus explained. 

Palpitation. — Palpitation of the heart has been defined as 

100 Cabot and Locke, Johns Hopkins Hosp. Bull., May, 1903. 



THE HEART 103 

an irregular or forcible heart action perceptible to the indi- 
vidual himself. In health, we are not ordinarily conscious of 
the action of our hearts, unless this action is much increased 
by exertion or by excitement. It seems probable that there 
are sensory nerves in the heart or in its vicinity which are 
stimulated under these circumstances. Pathological palpitation 
may be due either to an abnormal heart action or to an 
increased sensitiveness of these nerves, rendering the indi- 
vidual abnormally conscious of his heart's action. Naturally 
both causes may be operative in the same individual. 

An increased heart action does not necessarily produce 
the sensation of palpitation. This fact is frequently illustrated 
in cases of valvular disease, and is perhaps to be explained 
on the assumption that the gradual development of the con- 
dition allows the sensory nerves of the heart and adjacent 
structures to become accustomed to the changed conditions. 
Not infrequently, however, patients with hypertrophy and 
dilatation of the heart suffer from palpitation, especially during 
any exertion. In such cases the heart is working up to the 
limits of its capabilities, and possibly the increased tension of 
the cardiac wall stimulates the sensory nerves, and so produces 
the sensation of palpitation. 

In yet other individuals, no definite connection between the 
heart's action and the palpitation can be discovered. This is 
especially true of the palpitation associated with anaemia and 
that due to certain poisons, notably tobacco, tea, and coffee. 
In such cases it is possible that the systole is modified, but it 
seems more probable that the patient is conscious of his 
heart's action merely because of an increased irritability either 
of the cardiac nerves or of their centres. 

Cardiac Dyspnoea. — Shortness of breath is a very frequent 
symptom of heart diseases. It is often associated with a 
sensation of oppression about the chest or with a general 
feeling of anxiety, but it may occur alone. It may vary 



104 CLINICAL PATHOLOGY 

greatly in degree, from the slightest dyspnoea on exertion to 
the most extreme air-hunger, even when at perfect rest. This 
symptom is not characteristic of any one form of heart disease, 
but occurs whenever the interchange of gases in the lungs is 
seriously interfered with. Periodic interference with the inter- 
change of gases leads to periodic dyspnoea, the so-called cardiac 
asthma. 

The dyspnoea of heart disease is always due to an insuffi- 
cient interchange of gases between the blood and certain cells 
of the medulla. (See Chapter V.) Two causes are directly 
responsible for the dyspnoea of heart disease. The first is the 
slowing of the blood-stream, which diminishes the interchange 
of gases in the lungs and in the respiratory centre of the 
medulla. Any slowing of the blood-stream in the lungs 
beyond a certain limit leads to an insufficient interchange of 
gases. (See Chapter V.) A second cause for the dyspnoea 
of heart disease lies in the changes which take place in the 
alveolar epithelial cells of the lungs. These changes, which 
have already been described (see p. 58), would undoubtedly 
interfere with the interchange of gases in the lungs, even 
though the blood-stream were not retarded. 

The dyspnoea which develops only when the patient exerts 
himself is due to a relatively slow circulation, the rate of flow 
not being increased proportionately to the demands for fresh 
blood. Indeed the exertion may cause a fall of arterial press- 
ure in patients with heart disease. 101 

The term cardiac asthma is applied to those paroxysms of 
extremely severe dyspnoea which occur in individuals who have 
heart disease. The dyspnoea is often of the most extreme 
grade, and may be accompanied by excessive anxiety and a 
terrible sense of impending death. The paroxysms may begin 
after a meal, after exercise, during the night, or without any 
apparent cause. They occur most frequently in those who 

101 Buttermann, Arch. f. klin. Med., vol. lxxiv. p. I. 



THE HEART 105 

have arteriosclerosis or chronic nephritis. During the attack, 
the pulse is usually rapid, soft, and irregular in force and fre- 
quency. The blood-pressure is usually lower than normal. 
The most frequent cause of cardiac asthma is a transient weak- 
ness of the left ventricle. This raises the pressure in the 
pulmonary vessels, and so increases the work of the right 
heart. If the latter is unable to accomplish the additional 
work so thrown upon it, there results a diminution in the 
velocity of the general blood-current. It is difficult to say to 
what extent the universal and sudden overfilling of the pul- 
monary capillaries contributes toward the production of the 
symptoms. In certain cases the dyspnoea becomes less when 
the right heart weakens. Since the pulmonary capillaries 
would then be less distended, this favors the view that the 
distention of the capillaries is to some degree responsible for 
the paroxysms of dyspnoea. 

Patients suffering from heart disease frequently develop 
dyspnoea from pulmonary complications, such as bronchitis, 
pneumonia, and oedema, to which diseases they are, indeed, 
peculiarly subject. 

In the French literature, many other causes for the 
dyspnoea of heart disease are enumerated, among which are 
toxic and reflex influences. At present, however, there is little 
real proof for the existence of such causes. 

Cardiac Pain. — As has already been stated, a feeling of 
intense anxiety often accompanies cardiac dyspnoea. This 
feeling may occur alone, or it may be associated with pain in 
the precordium. The latter, however, rarely occurs alone, 
except in nervous individuals, in whom the pain is of psychic 
origin and is simply referred to the periphery. 

Cardiac pain, originating in the heart itself, is seen espe- 
cially in disease of the coronary arteries and of the first part 
of the aorta. It accompanies aortic more frequently than 
mitral lesions, because the former are more frequently asso- 



106 CLINICAL PATHOLOGY 

ciated with arteriosclerosis. Patients with various forms of 
myocarditis also frequently complain of pain about the heart 
and of cardiac distress, which sensations may either be con- 
stantly present or may occur in paroxysms. 

The severity of the pain varies greatly. On the one hand, 
the patient complains of sensations which trouble him mainly 
because they are unusual, while, on the other hand, the pain 
is of such indescribable severity that death seems imminent. 
It is not the place here to enter into a description of the 
clinical features of these cases of angina pectoris. They occur, 
almost without exception, in those who have sclerosis of the 
coronary arteries. The attack may come on without any 
apparent cause, but usually it is precipitated by some unwonted 
excitement, by overexertion, or by digestive disturbances. 
Most of the attacks are due to cardiac weakness induced by 
these unfavorable circumstances. 

We do not know what causes the pain of angina pectoris. 
Arteriosclerosis of the coronary arteries is certainly present 
in most cases, frequently causing a narrowing of the lumen 
of the vessel. 102 Perhaps it is the anaemia of certain parts 
of the heart which causes the pain. Such a theory finds an 
analogy in the condition known as intermittent claudication, 
in which, owing to a narrowing of the arteries, pains and 
disturbances of function develop in the legs whenever the 
patient walks some little distance. 103 In some cases the 
anginal paroxysms cease, and this has been attributed to a 
reopening of the vessel, although we have no proof for such 
an hypothesis. Breuer 104 calls attention to the fact that we 
are not yet perfectly clear even about intermittent claudication, 
for we do know how great a role spasmodic contraction of 
the arteries may play in this condition. Nothnagel 105 believes 

102 Curschmann, Kongr. f. in. Med., 1891, p. 275. 

103 Erb, Munch, med. Wochenschr., 1904, p. 905. 

104 Munch, med. Wochenschr., 1902, Nos. 39-41. 

105 Ztft. f. klin. Med., vol. xix. p. 209. 



THE HEART 107 

that the pain may originate from the vessels themselves. Such 
an hypothesis, attributing the pains of angina directly to the 
spasmodically contracted vessel, is very attractive. It would 
explain the fact that these paroxysms of pain may occur with- 
out anatomical disease of the coronary vessels, as has been 
observed in nervous individuals and especially in those who 
use tobacco to excess. Many other questions in relation to 
angina are still unanswered, as, for example, the reason why 
the pains radiate to the left branchial plexus, the cause of the 
syncope in some cases, and finally the cause of the sudden 
death. Every attack of true angina is a menace to the life of 
the individual, and not infrequently the patient dies during 
the attack. In only one other condition do we see an equally 
sudden death, and that is in coronary embolism. The body 
may be found in the exact position that it was in when the 
attack of angina began. No signs of asphyxia are present. 
The cause of sudden death has never been explained. 



CHAPTER II. 

THE BLOOD-VESSELS AND THE LYMPH. 

The condition of the arterial walls and the width of the 
arteries exercise a considerable influence upon the flow of blood. 
If the arteries were all fully dilated, it would be absolutely im- 
possible for the heart to maintain the circulation, for the rela- 
tively small quantity of blood in the body could not properly 
fill the vessels. The width of the arteries is regulated mainly 
by reflexes coming from various parts of the body. Stimula- 
tion of a peripheral nerve will normally cause a reflex arterial 
constriction and will raise the blood-pressure; and nervous 
impulses from the heart are also able to affect the size of the 
blood-vessels, and so in a measure to regulate the work of that 
organ. 

We have stated that the degree of contraction of the ar- 
teries, their tonus, is mainly dependent upon the nervous im- 
pulses that they* receive. Though recent observations have 
demonstrated an independent muscular tonus in the blood- 
vessels, this seems to play a very small part in health and 
disease. 

If the arteries leading to a certain part of the body dilate 
or contract, the blood-supply to that part will be altered. These 
changes are fully discussed in the ordinary text-books on physi- 
ology and pathological anatomy, and need not be dwelt upon 
here. It is necessary to remember, however, that, if the tonus 
of extensive vascular areas is altered, the effect is not easily 
neutralized by a change of tonus in the opposite direction in 
other parts of the vascular system, and that then the total 
peripheral resistance and perhaps the blood-pressure will be 
affected. For this reason, the condition of the numerous ab- 
dominal vessels, innervated by the splanchnic nerves, is of 
1 08 



BLOOD-VESSELS AND LYMPH 109 

primary importance in the maintenance of the peripheral re- 
sistance, and it is quite possible that the cutaneous vessels like- 
wise play an important role in man. 

The Arterial Blood-Pressure. — (The blood-pressure in the 
larger arteries is dependent mainly upon two factors, — the 
amount of blood pumped into the arterial system by the heart, 
and the resistance offered to the escape of blood from this 
system through the smaller arteries and capillaries. Of less 
importance is the elasticity of the vessel walls and the total 
quantity of blood in the body. These various factors, influ- 
encing blood-pressure, may interact upon each other in the most 
complicated manner. For example, if the arterial pressure be 
increased from any cause, the vagus nerve is stimulated, with 
the result that the heart is slowed and less blood is delivered 
into the aorta. In a like manner, when the volume of blood 
is rapidly changed, the blood-vessels change their caliber, so 
that, within certain limits, the blood-pressure is not altered. 

Systolic and Diastolic Pressures. The Pulse-Pressure. — 
The arterial pulse is caused essentially by the variations of 
pressure within the artery, produced by the intermittent ex- 
pulsion of blood from the heart. The highest point on this 
wave of arterial pressure is called the systolic pressure, and the 
lowest point the diastolic pressure. The difference between the 
two — i.e., the variation of pressure with each pulse — is called 
the pulse-pressure. Thanks to modern instruments, it is now 
possible to determine these pressures with a fair degree of 
accuracy upon man by indirect methods. 1 

The factors which influence the blood-pressure as a whole 
have been mentioned in the preceding paragraph. Of special 
interest, however, are the factors that affect the difference be- 
tween the systolic and the diastolic pressure, — i.e., the pulse- 
pressure. It is theoretically possible that this should be in- 

1 See Janeway, Clinical Study of Blood-Pressure, p. 77; Erlanger, 
Am. Jour, of Physiol., vol. x. 



110 CLINICAL PATHOLOGY 

fluenced in at least three ways. An increase in the amount of 
blood delivered at each beat from the heart into the aorta would 
tend to increase the difference between the diastolic and systolic 
pressures. On the other hand, a rapid emptying of the blood- 
vessels would likewise tend to increase this difference, inde- 
pendently of whether the extra blood flowed through the capil- 
laries into the veins, or whether it regurgitated into the heart 
owing to an aortic insufficiency. It is obvious that the amount 
of blood pumped into the arteries and the amount which escapes 
from them in both directions must, in the long run, be approxi- 
mately equal, for otherwise large amounts of blood would ac- 
cumulate in, or disappear from, the arteries, as the case might 
be. Finally, the rigidity of the arterial walls will exert an 
influence upon the pulse-pressure. If the arteries were abso- 
lutely rigid tubes, the heart would be compelled to move the 
whole column of blood with each beat, and between beats the 
flow would stop entirely. There would therefore be a high 
pressure in the arteries during systole and practically no press- 
ure during diastole, and the pulse-pressure, or the difference 
between the two, would be exceedingly high. There is reason 
to believe that slighter changes in the rigidity of the arteries 
will affect the pulse-pressure in a similar though less marked 
manner, and patients with arteriosclerosis frequently show high 
pulse-pressures. 2 

Some authors have attempted to estimate from the pulse- 
pressure the total output of blood from the heart, yet it is 
obviously impossible to do this so long as we cannot allow for 
the effect produced by the elasticity of the arterial walls, which 
latter varies not only in different individuals from such causes 
as arteriosclerosis, etc., but probably can also vary in the same 
individual under different conditions of absolute blood-pressure 
and of fulness of the artery. In spite of these objections, how- 
ever, it is possible that the determination of the pulse-pressures 
2 A. D. Hirschfelder, Personal Communication. 



BLOOD-VESSELS AND LYMPH 111 

will in the future furnish us with valuable data as to the quan- 
tity of blood being propelled by the heart. 

Physiological Variations in Blood-Pressure. — Age influ- 
ences the blood-pressure. During the first year of life the 
systolic pressure usually ranges between 75 and 90 mm. of mer- 
cury, in adults it is usually 100 to 130 mm., and in old people 
130 to 145 mm. 3 Excitement generally causes a most marked 
rise of pressure. Muscular exertion will also usually increase 
the systolic pressure, though this increase is less marked when 
the individual is expert in performing any particular act, and, 
indeed, it may then not take place at all. During exercise 
the difference between the systolic and diastolic pressures is 
often quite markedly increased, an indication, apparently, of 
the larger quantity of blood delivered by each systole of the 
heart. In the early hours of sleep, there is quite a marked 
fall in the mean blood-pressure, which gradually rises toward 
morning. 4 

Pathologically Increased Blood-Pressure. — Certain drugs 
may raise the blood-pressure either because they act mainly 
upon the heart, as does digitalis, or because they tend to cause 
a constriction of the blood-vessels, as does adrenalin. Acute 
asphyxia or acute anaemia of the medullary centres of the brain 
will stimulate the vasomotor centre most powerfully, producing 
a contraction of the splanchnic vessels and a great rise of 
arterial pressure. Such a cerebral anaemia appears to be the 
cause of the extremely high blood-pressures sometimes seen in 
cases of acute cerebral compression, a subject which will be 
discussed in another place (p. 450) . Lead colic is usually asso- 
ciated with a high arterial pressure, and the early stages of 
peritonitis are likewise frequently accompanied by such a rise. 
Pain, even that caused by pinching the skin, usually increases 
the systolic pressure in healthy individuals. 

'Janeway, loc. cit, p. 128. 

* Brush and Fairweather, Am. Jour, of Physiol., vol. v. p. 199. 



112 CLINICAL PATHOLOGY 

Continuous high pressure is seen in certain forms of renal 
disease (see p. 50). It may also accompany arteriosclerosis of 
the first part of the aorta or of the splanchnic vessels (p. 46). 
—Ed.) 

The effect of an increased peripheral resistance upon the 
general circulation depends for the most part upon the behavior 
of the left ventricle. If this were to act in an ideal manner, 
it would contract more forcibly, and so, by raising the general 
arterial pressure, would overcome the increased resistance. 
Unfortunately, however, when the peripheral resistance and 
the arterial pressure are much increased, the left ventricle does 
not empty itself completely, the pressure in the left auricle rises, 
and a retardation of the blood-flow through the lungs takes 
place. 

Pathological Diminution in Blood-Pressure. — Wide- 
spread dilatation of the blood-vessels may lead to a serious fall 
of arterial pressure and a slowing of the circulation, for, as we 
have said, the total quantity of blood in the body is insufficient 
to fill the blood-vessels properly if they are all widely dilated. 

Such a wide-spread dilatation may result from a general 
loss of arterial elasticity with stretching and widening of the 
blood-vessels. This has been observed in certain cases of aortic 
insufficiency (p. 59) and in the late stages of arteriosclerosis 
(p. 46). 

Arterial dilatation may also result from a wide-spread loss 
of arterial tonus. Thus, if the splanchnic vessels lose their 
tone, they become filled with blood, and the arteries to the other 
parts of the body, especially to the skin and muscles, are left 
comparatively empty. The patient becomes weak and pale, 
the arterial and venous pressures fall, and the heart receives an 
insufficient supply of blood. The pulse becomes soft and rapid, 
and finally syncope supervenes. Such a patient is practically 
bled into his own abdominal vessels, and life may last only a 
few hours or even minutes. If other arteries, in addition to 



BLOOD-VESSELS AND LYMPH 113 

the splanchnic vessels, are dilated, the symptoms are intensified ; 
yet the condition of the splanchnic vessels is of paramount 
importance on account of their great capacity. 

A clinical picture, similar to that just described, may be 
produced by toxic doses of such drugs as chloral and alcohol, 
both of which will ultimately paralyze the vasomotor centre. 
A similar picture is also presented by the so-called collapse that 
sometimes occurs during the course of infectious diseases. 
These symptoms are not those of ordinary heart failure, for the 
pulmonary congestion and the stasis in the veins of the general 
circulation are both lacking. The picture seems rather to be 
caused by an insufficient supply of blood without stasis, and it 
may be interpreted as an extensive vasomotor paralysis. 

This question has been carefully studied on animals. 5 The 
great falls in pressure which occur at the height of experimental 
infections with the pneumococcus, the diphtheria bacillus, and 
the bacillus pyocyaneus, have all been shown to be due to a 
paralysis of the vasomotor centres. In pneumococcus infec- 
tions, the heart may beat with more than its usual force, and 
may thus, to a certain degree, compensate for the loss of vaso- 
motor tone. In diphtheria infections, however, the heart is 
usually also injured, and some, indeed, claim that the injury 
to the heart is here the most important cause of the circulatory 
disturbances. 6 It has also been definitely proved that in a 
perforative peritonitis, experimentally induced, the cause of 
death is a toxic paralysis of the vasomotor and respiratory 
centres. 7 

To what extent these experimental results are applicable 
to man is somewhat uncertain. It is difficult to determine clin- 
ically whether the symptoms are due more to a cardiac weak- 

* Romberg, Passler, Bruhns, Miiller, Arch. f. klin. Med., vol. lxiv. p. 
652; Passler and Roily, ibid., vol. lxxvii. p. 96. 

'Steyskal, Ztft. f. klin. Med., vol. xliv. p. 368, and vol. li. p. 12Q, 
1 Heincke, Arch. f. klin. Med., vol. Ixix. p. 429. 
8 



114 CLINICAL PATHOLOGY 

ness or a vasomotor paralysis. Personally I am inclined to 
believe that both are at fault in most instances of circulatory 
failure during the course of acute infectious diseases. 

(The term " surgical shock" has been used to designate a 
peculiar depression of the activities of the central nervous sys- 
tem, which is ordinarily caused by very severe traumatism to 
the peripheral nerves. A slight or moderate traumatism to 
these nerves will ordinarily cause a rise in blood-pressure ; if, 
however, the injury be particularly severe or many times re- 
peated, or if the patient be weakened by anaemia, etc., then the 
result of the traumatism is a fall in blood-pressure, and the 
symptom-complex of shock is produced. Crile's exhaustive ex- 
periments 8 would seem to indicate that surgical shock is caused 
by an exhaustion of the vasomotor centre, which renders it 
unable to maintain the tonus of the arteries. The fall of blood- 
pressure is due, therefore, to a vasomotor paralysis, and the 
condition resembles in many particulars the collapse that may 
occur during the acute infectious diseases. — Ed. ) 

The Arterial Pulse. — The arterial pulse is produced mainly 
by changes of pressure within the arteries, caused by the inter- 
mittent expulsion of blood from the heart. In general, the 
frequency and rhythm of the pulse is the same as that of the 
heart, yet we must remember that some of the heart's beats may 
not reach the wrist, and that some may be retarded more than 
others in their passage to the periphery. Lesions of the heart 
may modify the form of the pulse, as is well illustrated in the 
typical pulses of aortic stenosis and aortic insufficiency; and 
the form of the pulse is also affected by the condition of the 
vessel wall. Many secondary waves on the main pulse-wave 
can be demonstrated by pulse tracings. Some of these are due 
to instrumental defects, and some to changes in the heart and 
vessels. Indeed, so many factors influence the form of the 
pulse-curve that it is usually quite impossible to draw any satis- 
8 Blood-Pressure in Surgery, 1903. 



BLOOD-VESSELS AND LYMPH 115 

factory conclusions from this form. We shall therefore omit 
a discussion of this subject. 

THE VEINS. 

Venous Stasis. — It has already been shown that stasis of 
the blood in the veins may result from cardiac weakness. The 
stasis in the pulmonary circulation, produced by a weakness of 
the left ventricle, may be overcome to a certain extent by the 
increased activities of the right ventricle, whereas the stasis in 
the veins of the general circulation, resulting from a weakness 
of the right ventricle, cannot be thus overcome, and the entire 
blood current is slowed. 

General venous stasis may also be caused by diseases of the 
lungs or by pressure upon the great veins. If the intrathoracic 
pressure be increased, either by a diminution in the elasticity 
of the lungs (emphysema) or by a collection of fluid or gas 
in the pleural cavities, or if the thoracic movements are les- 
sened, as happens during superficial breathing, then a diminu- 
tion in the flow of blood to the heart results. Pressure upon 
the great veins by tumors and especially by pericardial effu- 
sions may also interfere with the return of venous blood to the 
heart. A pericardial effusion may, indeed, cause sudden death 
by compressing the venae cavae just before their entrance into 
the right auricle, and so shutting off the entire blood-supply 
to the heart. 

Venous Murmurs. — In certain individuals, especially in 
chlorotic girls, a murmur may be heard over the bulbus jugu- 
laris. This is usually louder on the right than on the left side, 
and is known as the venous hum. Its cause is not well under- 
stood. Some believe that it is a murmur of stenosis caused by 
the passage of the blood from the external jugular vein into the 
jugular sinus, yet why this should occur especially in anaemic 
individuals is not known. Sahli ° considers that the blood 
8 Klin. Untersuchungsmethoden. 



116 CLINICAL PATHOLOGY 

flows more rapidly in anaemia, and that this is the cause of the 
murmur; yet it has not yet been satisfactorily proved that the 
blood-flow in anaemic individuals is really more rapid. 

THE MOVEMENTS OF THE LYMPH. 

The lymph may be looked upon as the fluid that has escaped 
from the capillaries. It carries material to the cells of the 
parenchyma, and, laden with waste products, returns to the 
blood again by way of the lymphatic vessels. Its composition, 
therefore, varies according to the organ from which it comes 
and according to the activity of that organ. 

We know of no disease in which too little lymph escapes 
through the capillary walls, although it seems probable that 
such do exist. 

CEdema. — Certain conditions lead to an accumulation of 
lymph in the lymphatic vessels and spaces, among which latter 
the serous cavities may be included. Theoretically, such ac- 
cumulations may be brought about, first, by an excessive forma- 
tion of lymph; secondly, by a hinderance to the escape of 
lymph ; and thirdly, by a combination of the two. The quan- 
tity of fluid that passes through the capillary walls depends, on 
the one hand, upon the difference in pressure between the blood 
in the capillaries and that of the lymph in the surrounding 
tissues, and, on the other hand, upon the permeability of the 
capillary walls themselves. 

CEdema from Stasis. — CEdema may be caused by a stasis 
of blood in the veins. This stasis may be merely local, as when 
it is caused by an occlusion of a vein by thrombosis or external 
pressure ; or it may be general, as when it results from patho- 
logical changes in the lungs, weakness of the right heart, intra- 
thoracic tumors, and pleural or pericardial exudates. The 
©edematous fluid that collects in the lymph-vessels and spaces 
in such cases, is poorer in proteids and leucocytes, but richer 
in erythrocytes, than is normal lymph. The organs that be- 



BLOOD-VESSELS AND LYMPH . 117 

come most swollen are those in which the tissues are under the 
least elastic tension and in which the venous stasis is favored 
by gravity. For this reason the oedema caused by general stasis 
is usually first observed about the ankles and over the lower 
part of the back. 

The mere obstruction of a vein does not necessarily lead 
to oedema, for a collateral venous circulation may be estab- 
lished. After the experimental ligature of a vein, the occur- 
rence of oedema is greatly favored by the frequent accompany- 
ing arterial hypersemia. 

Even an increased transudation of lymph does not neces- 
sarily cause an oedema, for the excessive amount may be carried 
away by the lymphatics. There must, therefore, be, in addi- 
tion, some interference to the lymph-flow from the part. When 
general venous stasis causes the oedema, the blood-pressure in 
the left subclavian vein is naturally raised, and this would 
furnish the interference to the flow of lymph into this vein from 
the thoracic duct. 

The lymph-flow may also be hindered in other ways. An 
increased pressure in the capillaries is transmitted to the tissues 
about them, which latter gradually become stretched and lose 
their elasticity. 10 This loss of elasticity diminishes the pressure 
normally exerted by the tissues upon the lymph-spaces, the 
difference between the blood- and the lymph-pressures is there- 
fore increased, and exudation is favored. On the other hand, 
the diminished pressure exerted by the tissues upon the lymph- 
spaces tends to lessen the rate of lymph-flow from the 'tissues 
toward the thoracic duct. For these reasons, the elasticity of 
the tissues exercises a most important influence upon the occur- 
rence of oedema, and different organs become swollen to dif- 
ferent degrees, even though they all are exposed to the same 
venous stasis. 

The mere obstruction of a lymphatic vessel rarely leads to 

10 Landerer, Die Gewebspannung, Leipzig, 1884. 






118 CLINICAL PATHOLOGY 

cedema, on account of the numerous anastomoses between the 
lymphatics. If, however, the thoracic duct be obstructed, as- 
cites and cedema of the legs usually develop. 

Inflammatory CEdema. — As is well known, inflammations 
injure the walls of the capillaries. There is an active local 
hyperemia, and, at the same time, a slowing of the blood-cur- 
rent caused by the changes in the vessel walls. These walls 
influence the amount and character of the transudate, and con- 
sequently the lymph of inflammation differs from that normally 
transuded, in that it contains more albumin and more numerous 
blood-corpuscles. Purulent inflammations are characterized 
by the richness of their exudates in leucocytes, which latter 
are attracted thither by the primary cause of the inflammation. 

Inflammatory processes also interfere with the removal of 
lymph from the tissues, for they directly diminish the tissue 
elasticity, with the results just described. Even the elasticity 
of tissues at some little distance from the inflammation may 
be diminished, so that these also become (Edematous, thus pro- 
ducing the so-called collateral cedema. 

Nephritic CEdema. — Of the dropsies that accompany ne- 
phritis, some are unquestionably due to simple stasis. We have 
seen that the heart is often weakened in nephritis, and it is 
obvious that this may cause the ordinary dropsy of heart dis- 
ease. We wish here, however, to consider those nephritic 
cedemas that occur independently of any cardiac weakness. 
They usually first appear in the subcutaneous tissues, and espe- 
cially in those that possess the least tension, as about the ankles 
and eyelids, though not infrequently the great serous cavities 
are early filled with fluid. 

CEdema of this character is rarely seen in certain forms of 
nephritis, especially in chronic interstitial nephritis, in the ne- 
phritides caused by certain poisons (arsenic), and in those 
associated with certain infectious diseases (pneumonia and 
typhoid fever). On the other hand, cedema is common and 



BLOOD-VESSELS AND LYMPH 119 

often of a most marked grade in chronic parenchymatous ne- 
phritis, in amyloid kidney, in scarlatinal nephritis, and in 
primary acute nephritis. 

The urine in these cases is frequently diminished in amount 
and rich in albumin; yet the high percentage of albumin can 
hardly be the cause of the cedema, for large quantities may be 
excreted with comparatively slight cedema, as sometimes hap- 
pens in amyloid disease of the kidney. Furthermore, a reduc- 
tion of the albumin in the blood cannot be the sole cause of the 
cedema, for we know that with plenty of food there is no 
diminution of albumin in these cases. When cachexia develops, 
the albumin may, indeed, be diminished and cedema may 
appear, but this cedema is of a different character and is of 
relatively slight extent. 

It is possible that the cedema of nephritis is produced by a 
primary retention of water in the body. In the forms of the 
disease under consideration, less urine than normal is usually 
secreted, and frequently the cedema increases as the urine di- 
minishes, and vice versa. Many writers, therefore, favor the 
view that a primary retention of water in the bodies of these 
patients dilutes their blood and so produces an hydrsemia or an 
hydremic plethora; and Hammerschlag has shown 11 that a 
diluted blood is usually present in these cases of nephritis. 
Nevertheless, the theory has many opponents. Most experi- 
menters have failed to produce an cedema by the mere infusion 
of salt solution. Half of the blood has been withdrawn and 
replaced in this manner and enormous quantities of fluid have 
been infused without producing any cedema. 12 Some other 
factor, therefore, seems to be necessary, and this is possibly an 
injury to the vessel wall. Magnus has discovered a whole 
series of substances which will produce extensive anasarca if 

" Ztft. f. klin. Med., vol. xxi. p. 475. 

" Cohnhcim and Lichtheim, Virch. Arch., vol. lxix. p. 106; Magnus, 
Arch. f. cxp. Path., vol. xlii. p. 250. 



120 CLINICAL PATHOLOGY 

injected into an hydremic animal. Among these are substances 
that are retained in the body after removal of the kidneys. 

One may assume, therefore, that some change in the capil- 
lary walls is, in part, responsible for the oedema of nephritis, 
though up to the present these changes have not been demon- 
strated anatomically. We have already seen that such hypo- 
thetical changes in the blood-vessels probably account for the 
cardiac hypertrophy in certain cases of nephritis. The oedema 
of nephritis is therefore explainable on the theory of primary 
retention of water in the body combined with an injury to the 
walls of the blood-vessels. 

The relation of the tissues to the oedema of nephritis is not 
well understood. Their elasticity might be primarily dimin- 
ished or their osmotic pressure might be increased, and in either 
case a retention of fluid could result. 13 These are possibilities 
which open a new field for investigation. 

(Some nephritic cedemas apparently depend upon the re- 
tention of sodium chloride in the body. The normal individual 
excretes this salt at about the same rate as it is ingested, so that 
the amount in the body remains nearly constant. In nephritis, 
on the other hand, the excretion frequently does not follow the 
same curve as the ingestion. 14 The French school, especially, 
has explained certain cases of nephritic oedema on the basis of 
a retention of chlorides in the body. According to this hypothe- 
sis, the inability of the kidneys to eliminate sodium chloride 
leads to a retention of this salt in the body, and this retention, 
in turn, necessitates an accumulation of water in the tissues in 
order to maintain the proper osmotic relations. In some cases 
of nephritis, 15 truly wonderful results have followed variations 
in the amount of common salt taken in the food. When large 

18 Strauss, Ztft. f. klin. Med., vol. xlvii. p. 337 ; Koziezkowsky, ibid., 
vol. li. p. 287. 

"Halpern, Festschrift f. E. Salkowski, Berlin, 1904. 

15 See, for example, that reported by Widal and Javal, International 
Clinics, Fourteenth Series, vol. i. p. I. 



BLOOD-VESSELS AND LYMPH 121 

quantities were given to such patients, the kidneys did not 
excrete all of it, the weight of the body rapidly increased 
owing to the accumulation of water, and when this increase 
had reached a certain limit, oedema appeared. If now the 
sodium chloride in the diet were so reduced that the output 
exceeded the intake, then the water retained in the body was 
rapidly excreted and the oedema disappeared. Other variations 
in diet, such as changes from milk to meat, etc., did not in- 
fluence the oedema, except in so far as they were accompanied 
by changes in the quantity of common salt taken. From these 
observations, it seems very probable that certain nephritic 
oedemas depend upon a primary, insufficient elimination of 
sodium chloride by the kidneys. — Ed.) 

Other (Edemas. — We know little concerning the dropsies 
caused by severe cachexias and by many diseases of the cord 
and of the peripheral nerves. Changes in the composition of 
the blood probably contribute to the causation of the former, 
while in the latter, paralyses of the muscles would interfere 
with the movements of the lymph and so tend to produce 
oedema. Yet in neither case do these seem to be the sole causes. 

Composition of Exudates. — The composition of exudates 
varies with their origin. 16 Those due to inflammatory causes 
usually contain four per cent, of albumin or over, while those 
due to other causes usually contain between o.i and 0.8 per 
cent. The exudates that are poorest in albumin are those 
caused by cachexias and by chronic nephritides, a percentage 
less than 0.1 being rarely found except in serious renal disease, 
especially in amyloid disease of the kidney. 

Chylous and Chyliform Ascites. — Exudates into the peri- 
toneal cavity, and more rarely those into the pericardial and 
pleural cavities, may contain considerable amounts of fat. 
This may arise from a fatty degeneration of the cells of the 
exudate, with subsequent disintegration of these cells. When 

10 Hoffmann, Arch. f. klin. Med., vol. xliv. p. 413. 



122 CLINICAL PATHOLOGY 

the blood contains such large quantities of fat, the latter some- 
times passes through the capillary walls into the exudate. 
Such exudates into the peritoneal cavity are called chyliform 
ascites. 17 

In another group of cases, usually caused by carcinomata, 
the abdominal lymphatics rupture and the chyle flows directly 
into the peritoneal cavity, producing the so-called true chylous 
ascites. The composition of the ascitic fluid then depends 
largely upon the character of the food, and when certain fats 
are ingested, they may be demonstrated in the ascitic fluid. 18 
During life it is often impossible to differentiate these two 
forms of ascites. 

Pulmonary CEdema. — (Edema of the lungs may result 
from the same causes as does oedema of other parts of the body. 
The exudation about an inflammatory area corresponds to the 
inflammatory cedema already described (p. 118). On account 
of the rich and peculiar blood-supply of the lungs, however, a 
local cedema from stasis does not occur. If there be a hinder- 
ance to the blood-flow through one part of the lungs, the blood 
merely takes another course. No sharp line can be drawn be- 
tween local inflammatory cedema of the lungs and a small pneu- 
monic patch. 

Of great interest is the cause of the general pulmonary 
cedema that so frequently terminates cardiac, pulmonary, and 
infectious diseases. Two hypotheses have been advanced in 
explanation of this cedema. The first considers that it is 
caused by stasis. If, experimentally, the left ventricle of an 
animal be seriously injured while the right is left intact, then 
pulmonary oedema frequently develops. 19 The cedema in such 
instances is evidently caused by stasis, and we have reason to 

17 Bargebuhr, Arch. f. klin. Med., vol. li. p. 161 ; Pagenstecher, D., 
Ztft. f. Chir., vol. Ixii. p. 312; Mutermilch, Ztft. f. klin. Med., vol. xlvi. 
p. 123. 

"Minkowski, Arch. f. exp. Path., vol. xxi. p. 373. 

19 Cohnheim and Welch, Virch. Arch., vol. lxxii. p. 373. 



BLOOD-VESSELS AND LYMPH 123 

believe that at least some pulmonary oedemas of man have a 
like causation. This, in all probability, is the cause of the 
cedema that sometimes develops after sudden, severe injury to 
the left heart, such as may be produced, for example, by an 
acute aortic insufficiency. 

In order to produce this cedema experimentally, it is neces- 
sary that the left ventricle should be almost completely para- 
lyzed; for if it be only relatively weakened, no cedema of the 
lungs ensues. 20 Now the general arterial pressure of patients 
with pulmonary cedema, especially when the latter follows 
nephritis or arteriosclerosis, rarely reaches the low level that is 
experimentally necessary, and in these patients there is certainly 
no complete paralysis of the left ventricle. Sahli, therefore, 
believes that general pulmonary cedema results, in most in- 
stances, from changes in the capillary walls. A number of 
facts support this view. First, the cedema is unevenly dis- 
tributed throughout the lungs; and secondly, it is often asso- 
ciated with definite inflammatory processes. Indeed, in heart 
disease, no sharp line can frequently be drawn between the 
cedematous areas and the pneumonic patches that are so fre- 
quently encountered. Some cedemas of the lungs are therefore 
almost certainly of an inflammatory nature. Possibly future 
observations on the percentage of albumin in the cedematous 
fluid will give some indication as to the nature of its cause. 

Though it must be acknowledged that inflammatory pro- 
cesses do contribute to the production of certain pulmonary 
cedemas, nevertheless it seems to me that the weakness of the 
left ventricle is of, at least, equal importance in most cases. 
The results of animal experimentation are not directly appli- 
cable to man. The chronic pulmonary stasis that accompanies 
heart and kidney diseases may induce changes in the walls of 
the capillaries of the lungs, so that a relatively slight weakness 

20 Sahli, Ztft. f. klin. Med., vol. xiii. p. 482; Arch. I exp. Path., vol. 
xix. p. 433. 



124 CLINICAL PATHOLOGY 

of the left ventricle could produce oedema, which would not be 
the case if the vessels were entirely healthy. Not infrequently 
the physician sees patients in whom a weakening of the left 
ventricle is followed by an oedema of the lungs and a subsequent 
strengthening of the ventricle by a disappearance of the oedema. 



CHAPTER III. 

THE BLOOD. 

General Considerations. — The pathology of the blood is 
intimately connected with that of every individual organ in 
the body; for it is the connecting link between all of them, 
receiving material from and giving material to each. Its con- 
stitution depends, therefore, to a great extent, upon the condi- 
tion of the various parts of the body. It contains a great 
variety of substances; yet the rapidity of the blood-current, 
the minute quantities of many of these present, and the rapid 
excretion of those which are present in excess allow the blood 
to maintain a fairly constant composition. 

It is improper to designate any one or any several organs 
as the blood-forming organs. Every tissue in the body fur- 
nishes its contribution to the blood, and when an organ is 
spoken of as a blood-forming organ it is usually meant that it 
gives to the blood some of its more striking elements, the blood 
corpuscles. 

From what has been said, it will be seen that the composi- 
tion of the blood will change whenever there are pathological 
changes in the activity of any organ that furnishes metabolic 
products to the circulation. Viewed from this stand-point, 
there are a great number of blood diseases, among them dia- 
betes and the majority of hepatic and renal disorders. Clini- 
cally, however, it is customary to speak of diseases of the blood 
only when the changes in the blood dominate the pathological 
picture, or when the cause of the blood changes is unknown. 
Whether, in the latter class of cases, the blood changes are 
really primary or not is a question that cannot at present be 
definitely decided. 

Changes in the blood-cells and in the haemoglobin are recog- 

125 



126 CLINICAL PATHOLOGY 

nized with comparative ease, and consequently they are better 
known than are the changes in the composition of the plasma. 

ANEMIA. 

Although the term anaemia is used to designate those condi- 
tions in which the haemoglobin or the red blood-corpuscles, or 
both, are reduced, it should not be assumed that these are the 
only changes of consequence in anaemic blood. Other altera- 
tions, of perhaps equal importance, take place in other constitu- 
ents, and a satisfactory understanding of anaemia will only be 
possible when we shall have become acquainted with all these 
various changes. For example, the integrity of the red cor- 
puscles is intimately dependent upon the molecular concen- 
tration of the plasma. If they be placed in solutions which 
contain either too large or too small a quantity of salts, they 
become either shrunken or swollen, and in either case they 
may lose their haemoglobin. The proteids of the plasma also 
seem to have some influence upon the property of the red cells 
to retain their haemoglobin ; and the presence of certain poisons 
in the blood will undoubtedly cause a discharge of the haemo- 
globin from the stromata of the corpuscles. 

Anaemia from Hemorrhage. — Anaemia may be due to an 
acute hemorrhage. If the loss of blood exceed a certain limit, 
which is about fifty per cent, of the total quantity, then the 
amount left in the vessels is insufficient for the maintenance of 
the circulation, and the patient dies with all the symptoms of 
acute asphyxia, owing to the insufficient supply of blood to the 
tissues and especially to certain parts of the brain. This sub- 
ject of acute asphyxia will be discussed in the chapter on 
respiration. 

If the hemorrhage does not exceed this limit, the fluid por- 
tion of the blood lost is rapidly replaced by fluids from the 
tissues and food. The proteids and the corpuscles are replaced 
more gradually by an increased functional activity on the part 



THE BLOOD 127 

of the tissues which furnish them ; and finally, after weeks, or 
perhaps months, the blood regains its normal composition. 
During the first few hours after a hemorrhage, therefore, the 
blood, as a whole, is reduced in quantity. Then follows a 
dilution of that present with lymph ; and after this there comes 
the regeneration of the red corpuscles. The regenerated cor- 
puscles are often smaller than normal, but some may be- 
enlarged and a few of them may contain nuclei. For a con- 
siderable period after the hemorrhage, the individual corpuscles 
contain less haemoglobin than do normal ones, for this pigment 
is regenerated comparatively slowly, and for some time, there- 
fore, the proportion between the percentage of haemoglobin 
and the number of red corpuscles remains less than the normal 
proportion. The leucocytes in the peripheral blood are usually 
increased in number for a short period after the hemorrhage. 
The rapidity with which the blood is regenerated depends in 
part upon the amount of blood lost, in part upon the general 
nutrition of the patient, and in part upon the treatment which 
he receives. 

General Considerations Relative to the Chronic Anaemias. 
— In the chronic anaemias the blood does not return so quickly 
to the normal, because the cause of the anaemia remains opera- 
tive. This cause may injure either the blood-forming organs 
or the blood-corpuscles already formed. It is well known that 
the blood of one animal may destroy the corpuscles of another, 
and we must admit the possibility that similar toxic substances 
may develop in the body under pathological conditions. In- 
deed, there is evidence that this does occur in certain diseases. 1 
Various poisons, such as chloroform and potassium chlorate, 
exert a similar injurious action upon the red blood-cells. It is 
also possible that an anaemia may be produced by an accelera- 
tion of the normal destruction of the red blood-cells, which 
becomes so rapid that the normal regenerative processes cannot 

1 Maragliano, Kongr. f. in. Med., 1892, p. 152. 



128 CLINICAL PATHOLOGY 

keep pace with it. Practically the same condition is produced 
when repeated, small hemorrhages take place, for here again 
the loss of blood may be so great that the normal regenerative 
processes cannot supply the deficiency. 

On the other hand, the anaemia may arise, not from an 
excessive loss or destruction, but from an insufficient forma- 
tion of red blood-corpuscles, and it is often extremely diffi- 
cult in the individual case to determine which of the two is 
primary. An increase in the amount of iron deposited in the 
liver would indicate an increased destruction of red corpuscles. 
This organ normally contains a small amount of iron, but in 
anaemia the amount is often greatly increased ; and not infre- 
quently the spleen, kidneys, and bone-marrow also show ab- 
normal deposits of iron salts. In the anaemias that are caused, 
not by destruction, but by losses of blood through hemorrhage, 
such deposits do not occur ; 2 and, indeed, the iron normally 
present in the tissues may be reduced, for it is utilized in the 
formation of new corpuscles. An increased excretion of pig- 
ments derived from the haemoglobin, — viz., bilirubin and uro- 
bilin, is also to a certain extent indicative of an increased de- 
struction of the erythrocytes. 

The red blood-corpuscles themselves frequently show 
changes in anaemia. In the first place, they may be of irregu- 
lar shape, so that hardly any two look alike (poikilocytosis). 
Then they may vary greatly in size, some being extremely 
small, the so-called microcytes, while others are extremely 
large, the so-called macrocytes. Finally, they may show clear 
spaces in their protoplasm (endoglobular degenerations). All 
of these changes are of a degenerative character. 3 

The staining properties of the red blood-corpuscles may 
also be altered. Normally they stain evenly but somewhat more 
intensely toward the periphery. In the bone-marrow the very 

2 Stiihlen, Arch. f. klin. Med., vol. liv. p. 248. 

3 Weintraud, Virch. Arch., vol. cxxxi. p. 497. 



THE BLOOD 129 

young forms often take up several abnormal tints when stained 
with certain complex stains; i.e., they are polychromatophilic. 
It seems probable that degenerating cells may exhibit similar 
abnormalities in their staining properties. This abnormal af- 
finity for certain pigments may affect the entire cell, or it may 
be limited to certain granulations. 4 The latter, known as 
granular basophilia, is particularly well marked in the anaemia 
of chronic lead poisoning. The old strife as to whether 
polychromatophilia is a sign of degeneration or of regenera- 
tion seems to have given way to the view that it may indicate 
either; although in time it is possible that we shall learn to 
recognize differences which will serve to distinguish the two 
modes of origin. 

In certain forms of anaemia the quantity of haemoglobin is 
relatively greater than the number of red corpuscles, whereas 
more commonly it is relatively less. In still other conditions, 
the corpuscles contain abnormal amounts of water, even though 
there be no change in the percentage of water in the plasma. 

The presence of nucleated red blood-corpuscles in the cir- 
culation is usually indicative of an increased formation of 
these cells. Such nucleated red cells are found normally only 
in the tissues in which erythrocytes are produced, — viz., the 
red marrow of the bones and, during fetal life, the liver and 
spleen. The red cells that pass into the blood normally have 
already lost their nuclei. When regeneration is very active, 
however, immature, nucleated, red cells escape into the circula- 
tion. (No absolutely strict parallelism exists between the num- 
ber of nucleated erythrocytes in the peripheral blood and the 
amount of regeneration in the bone-marrow. On the one hand, 
as in " aplastic anaemia," nucleated cells may appear in the 
blood, even though there is a diminished formation of red 
cells in the marrow ; whereas, on the other hand, nucleated 
cells may be absent from the peripheral circulation for weeks, 

* Colin, Munch, mcd. Wochens., 1900, No. 6. 
9 



130 CLINICAL PATHOLOGY 

even though, as in pernicious anaemia, we have every reason to 
believe that their formation is increased.— Ed.) In very severe 

anaemias we may find nucleated red cells of normal size, the 

so-called normoblasts,— together with those of large size, 

megaloblasts. The presence of the latter has been regarded by 
many 5 as an indication that the formation of the red cor- 
puscles has returned to the embryonal type. For reasons which 
will appear in the discussion of pernicious anaemia, we prefer 
to regard these cells merely as the products of any exceedingly 
rapid regeneration of red corpuscles. According to the ob- 
servations of Engel, 6 furthermore, these megaloblasts have 
nothing whatever to do with the embryonal red cells. 

The red bone-marrow is increased in quantity in many 
forms of anaemia. Normally this tissue is limited to the flat 
bones and the extremities of the long bones. If, however, the 
necessity arises for a greater production of red cells, then the 
red marrow spreads over many bones, the change being in the 
nature of a compensatory process. We are among those who 
believe that all increases of red marrow are of this nature, and 
that there is no necessity for making a division between nor- 
mal and pathological red marrow. 

Chlorosis. — Certain forms of chronic anaemia are suffi- 
ciently well defined to be distinguished clinically. Of these, 
we shall first consider chlorosis. This occurs usually, perhaps 
exclusively, in girls at about the time of puberty. Its cause is 
not well understood. Unsanitary surroundings are certainly 
not the sole causative agents, for the disease occurs with about 
equal frequency among the upper as well as the lower classes. 
Some have ascribed chlorosis to disturbances of the nervous 
system, others to diseases of the female genitalia, but both, it 
seems to me, without sufficient evidence. 

6 Rindfleisch, Virch. Arch., vol. cxxi. p. 176; Ehrlich, Kongr. f. in. 
Med., 1892, p. 33 ; H. F. Miiller, Arch. f. klin. Med., vol. li. p. 282. 
8 Die klinische Untersuchung des Blutes, Berlin, 1900. 



THE BLOOD 131 

The color of the skin in chlorosis usually varies from a 
slight pallor to the typical, pale, greenish tint. The face, how- 
ever, may be of an unusually brilliant color (chlorosis rubra). 
At times the patient is emaciated, more frequently, however, 
the fat is well preserved. The nervous symptoms present are 
for the most part, caused by the anaemia. 

The blood always shows a diminution in the quantity of 
haemoglobin to the unit-volume, and the individual red cor- 
puscles are usually paler than normal. Many of them are of 
small size, and some are deformed in shape. In severe cases, 
nucleated red corpuscles may be present, being either of normal 
size or very exceptionally of the megaloblastic type. 7 In some 
cases, the number of red corpuscles is normal, but usually it is 
moderately diminished, v. Limbeck 8 states that, of two hun- 
dred and seventy-nine cases of chlorosis, only one hundred and 
five, or thirty-seven per cent., showed no diminution in the 
number of the red corpuscles. 

That the amount of haemoglobin is diminished has been 
demonstrated by colorometric, spectrophotometric, and chemi- 
cal methods. The dried blood may show 0.03 per cent, of 
iron instead of the normal 0.06 per cent. 9 And although these 
results have been more recently questioned, 10 it does not appear 
to me that the method of obtaining the red corpuscles was one 
which is free from objection. 11 

As in other anaemias, the volume of the red cells is also 
changed. 12 In chlorosis, the leucocytes do not vary greatly 
from the normal. The percentage of water in the serum is 
approximately normal in the milder cases, whereas in the more 

T Hammerschlag, Wien. med. Presse, 1884. 

• Klin. Path, des Blutes. 

* Becquerel and Rodier, Unters. ii. d. Zusam. d. Blutes, 1845. 

10 P.iernacki, Ztft. f. klin. Med., vol. xxiv. p. 460. 

11 See, also Wendelstadt u. Bleibtreu, Ztft. f. klin. Med., vol. xxv. p. 
363- 

" Kossler, Zentralbl. f. in. Med., 1897, No. 26. 



132 CLINICAL PATHOLOGY 

severe ones it is increased. 1 - 3 The total quantity of blood in 
the body seems considerable. 14 Of other changes in the serum 
we know little. From the fact that patients with chlorosis 
show a tendency to the formation of venous thrombi, it has 
been assumed that their blood contains larger amounts of 
fibrin ferment, an assumption, however, which is incorrect. 15 
Not infrequently there is a retention of water in the body of 
chlorotic patients, but its cause is not well understood. 

Autopsies upon patients with chlorosis are few in number, 
and these have shown surprisingly little that was abnormal. 16 
No degenerative changes were present in the liver, heart, or 
kidneys, and no changes in the bone-marrow of the tibiae were 
found. Virchow observed a general hypoplasia of the heart 
and blood-vessels, and especially a narrowing of the aorta, and 
these have been assumed to be causative agents in the produc- 
tion of the disease. This view, however, does not appear very 
reasonable, for it is difficult to understand how chlorosis could 
heal as completely as it does if this were its cause; and, fur- 
thermore, stenosis of the aorta is known to produce quite a 
different set of symptoms. 

Although chlorosis heals spontaneously in practically every 
case, the healing is greatly accelerated by the administration 
of iron. Indeed, proper food seems to be of secondary im- 
portance, for chlorosis may develop in individuals who have 
lived in the best of surroundings. The brilliant results achieved 
by the administration of iron are in themselves almost char- 
acteristic of this type of anaemia, for in no other form do we 
see such striking effects, save possibly in those anaemias which 
result from hemorrhages. 

The value of the administration of iron in chlorosis lends 

13 See Grawitz, Klin. Path, des Blutes. 

14 v. Jaksch, Ztft. f. klin. Med., vol. xxiii. p. 187 ; Stintzing u. Gumprecht, 
Arch. f. klin. Med., vol. liii. p. 265. 

15 Quenstedt, Diss. Tubingen, 1902. 
"Grawitz, Klin. Path, des Blutes, p. 279. 



THE BLOOD 133 

support to the theory that the cause of the disease is an inade- 
quate or improper formation of the red blood-corpuscles. We 
possess no evidence favoring the opposite possibility, — viz., 
that there is a pathological destruction of the red cells, for de- 
generative changes in the red corpuscles are not marked, jaun- 
dice does not occur, and the quantity of pigments in the urine 
and fasces is less than normal. These facts cannot be regarded 
as proof that there is no pathological destruction of red cells 
in chlorosis, but they certainly render it very improbable. Un- 
fortunately, we possess no evidence on the more decisive ques- 
tion as to whether or not there is an excessive deposit of iron 
pigment in the liver. Nevertheless, from the facts in our pos- 
session, we may assume that the underlying cause of chlorosis 
is an insufficient formation of red blood-corpuscles. 

The exact manner in which iron exerts a favorable effect 
upon chlorosis still remains unsettled. The patients, suffering 
from this disease, ordinarily show no marked digestive disturb- 
ances, although some, at least, seem to absorb fats poorly. 17 
There is likewise no conclusive evidence that their absorption 
of iron from the intestinal tract is less than normal, though the 
data upon this point are not very accurate. It is therefore diffi- 
cult to understand why the iron salts in the food, which are 
sufficient for all ordinary needs, are insufficient in chlorosis. 
It seems to me most probable that iron cures chlorosis by act- 
ing as a stimulant to the blood-forming organs, very much as 
docs arsenic in certain other forms of anaemia. 18 

Secondary Anaemias. — The remaining forms of anaemia are, 
for the most part, merely symptomatic of other pathological 
conditions. Where their causation is known, they are termed 
sec< mdary anaemias, in contradistinction to the so-called 
primary anaemias, whose causes are unknown. This classifica- 

™ Wallerstein, Diss. Bonn., 1890. 

"v. Noorden, Berl. Win. Wochens., 1895, Nos. 9 and 10; Hofmann, 
Virch. Arch., vol. cxl. i>. 235. 



134 CLINICAL PATHOLOGY 

tion into primary and secondary anaemias is serviceable, but 
hardly final, for it seems certain that, as we become better ac- 
quainted with the causation of anaemias, the number of cases 
assigned to the primary group will progressively diminish and 
the number classified as secondary anaemias will correspond- 
ingly increase. 

A great variety of causes may give rise to mild and mod- 
erately severe forms of secondary anaemia. Of these, we may 
first mention repeated hemorrhages, such as may occur from 
ulcer or from carcinoma of the stomach, from intestinal ulcer- 
ations, from hemorrhoids, from uterine myomata, etc. Sec- 
ondary anaemias may result, furthermore, from chronic poison- 
ing, as by lead or mercury, from gastro-intestinal disease, from 
malignant tumors, from infections such as tuberculosis, syphi- 
lis, and malaria, and from chronic diseases of the liver, kidneys, 
heart, or nervous system. It should be remembered, however, 
that none of these diseases necessarily give rise to an anaemia. 

It is still uncertain in what manner many of these diseases 
produce the anaemia. Infectious processes frequently injure 
the red blood-corpuscles directly, as may be inferred from the 
degeneration which they produce in these cells. Yet the de- 
struction of a few corpuscles, more or less, would hardly give 
rise to an anaemia, for considerable numbers would be imme- 
diately replaced by regenerative processes. In malaria, the 
Plasmodia certainly destroy the corpuscles in large numbers, 
and this seems to be the direct cause of the malarial cachexia. 
In nephritis, the reduction in the number of red cells per unit 
of volume may be due in part to a dilution of the blood, and 
in part, as in hemorrhagic nephritis, to repeated losses of blood 
in the urine. 

Insufficient nourishment will give rise to an anaemia in 
some cases. An absolute fast, even if continued up to death, 
merely causes a reduction in the total quantity of blood with- 
out any diminution in the haemoglobin or red curpuscles to the 



THE BLOOD 135 

unit of volume. If, after such a fast, food and liquids be taken 
in sufficient quantity, then water is rapidly added to the blood 
with a resulting reduction in the percentage of haemoglobin 
and in the number of red cells per unit of volume. The pro- 
longed use of food, deficient in some important constituent, 
will also cause an anaemia. For example, a continuous milk 
diet will have this effect, on account of the small quantity of 
iron in the milk. Especially injurious is the combination of 
improper food and continued hard work. Other favoring 
factors are care and worry, poor light, poor air, lack of sleep, 
etc. Patients with anaemia from such causes improve most 
markedly if their surroundings are improved; 19 and although 
their absorption of iron may be less than normal, 20 yet the 
simple administration of salts of this metal without a change 
in their surroundings has comparatively little effect upon their 
anaemia. 

Finally, mild and moderately severe secondary anaemias of 
this character may occur in patients who live under the best of 
hygienic surroundings, and we are unable to form any con- 
ception as to their cause. Many such individuals seem to 
feel perfectly well, so that one might almost question whether 
their anaemia was physiological or pathological. Others, how- 
ever, suffer from the same symptoms as do most anaemic pa- 
tients, these symptoms being especially marked upon exertion. 

The blood picture in the secondary anaemias may show 
considerable variations. In some patients the changes are 
hardly demonstrable, while in others they may be of the most 
extreme grade. 

Certain possible fallacies in the methods of blood examina- 
tion should be noted. In the first place, the ordinary examina- 
tion of the blood may show nothing abnormal, and yet there 
may be a reduction or an increase in the total quantity of blood 

"Grawitz, Klin. Path, des Blutcs, pp. 159-163. 

" Hosslin, Munch, med. Wochcns., 1890, Nos. 38 and 39. 



136 CLINICAL PATHOLOGY 

in the body. 21 On the other hand, it is possible that the blood 
may be of different constitution in different parts of the body, 
so that the cutaneous capillaries contain relatively few or rela- 
tively many corpuscles. Such possibilities of error cannot be 
easily eliminated in our clinical methods of blood examination. 

In secondary anaemia the red cells frequently vary in stain- 
ing properties (polychromatophilia) and in shape (poikilocy- 
tosis). The dimensions of the cells may vary more widely 
than in health, so that we find microcytes and megalocytes. 
Signs of rapid regeneration are also frequently met with, espe- 
cially nucleated red cells of normal size (normoblasts), and, 
very rarely, nucleated red cells of large size (megaloblasts). 
All these changes are dependent rather upon the severity of the 
anaemia than upon its cause. As a rule, the white cells are 
normal unless some special cause for a leucocytosis is present. 
Changes in the blood-serum will be considered in another place. 

Pernicious Anaemia. — In the third form of anaemia, the so- 
called pernicious form, the variation in the red cells reaches its 
maximum. Their number is greatly reduced, and Quincke has 
reported a case in which only one hundred and forty-three thou- 
sand per cubic millimetre were counted. The haemoglobin is 
also markedly diminished, although, as a rule, it is relatively less 
reduced than is the number of the red corpuscles ; in other 
words, the average red corpuscle contains as much or more 
coloring matter than normal ones do. Poikilocytosis becomes 
extreme. At times, only a small proportion of the red cells 
present a normal appearance. The majority show some one or 
other of the many changes which have already been described. 
Nucleated red cells are especially numerous, the most char- 
acteristic and often the predominating form being the megalo- 
blasts. The nuclei of these cells are often found in the process 
of division. The leucocytes are only rarely increased ; usually 
their number is normal or is diminished. 

21 Stintzing and Gomprecht, Arch. f. klin. Med., vol. liii. p. 287. 



THE BLOOD 137 

As a rule, in pernicious anaemia, the blood-serum is not 
particularly deficient in solids. 22 Grawitz found, however, 
that such a deficit is apt to be marked in those cases of severe 
anaemia which are due to malignant tumors or to chronic 
infectious diseases. Indeed, he has shown experimentally 
that pieces of carcinoma introduced into the circulation of 
animals will attract lymph and thereby cause a dilution of the 
blood-plasma. The weight of the total solids of the blood 
is always markedly diminished, owing to the small number 
of corpuscles. The total amount of blood in the body also 
appears to be less than normal, if we may judge from the 
impressions received at the bedside and at autopsy. 

The effects of a very severe anaemia upon the patient are 
often most striking. His brain and muscles are easily fatigued, 
he suffers from shortness of breath and from fainting spells; 
gastric secretion is diminished or entirely absent. There is 
often a great tendency to bleeding, especially into the skin and 
retinae. Fatty degeneration of various organs is the rule, it 
being especially marked in the liver, the kidneys, and, above 
all, in the heart muscle. Not infrequently fever is present, due 
possibly to substances liberated from the disintegrated red 
blood-corpuscles, but as to this there is still some uncertainty. 

Very remarkable changes are found in the central nervous 
system in pernicious anaemia. 23 The most frequent anatomi- 
cal lesion is degeneration of the posterior columns of the spinal 
cord, though the lateral columns and the gray matter may 
also be diseased. 24 The cause of these changes is still uncer- 
tain. Some believe that they are caused by the anaemia, others 
that they are due independently to toxic influence. 

The pernicious form of anaemia must be regarded merely 

"Hammcrschlag, Ztft. f. Klin. Med., vol. xxi. p. 478 ; Grawitz, Klin. 
Path, <!<■-; Blutes, i>. 215. 

; Lichtheim, Kongr. f. in. Med.,' 1887, p. 84. 

" Teichmuller, Ztft. f. Nervenheilk., vol. viii. p. 385- 



138 CLINICAL PATHOLOGY 

as a symptom-complex which may be caused by a variety of 
pathological processes. For a certain group of cases no cause 
has yet been found, and to this group is given the name of 
essential pernicious anaemia, or the Biermer or Addison type 
of anaemia. Such cases appear to be especially frequent in 
certain localities, — e.g., Switzerland. 

The blood-picture which we have described was at one 
time regarded as characteristic of this essential pernicious 
anaemia of unknown causation; yet time has shown that the 
same blood-findings may be present in anaemias of known 
origin. There has been a continual endeavor on the part of 
certain investigators to differentiate these two forms of per- 
nicious anaemia, and special emphasis has been laid upon the 
presence of megaloblasts as favoring the diagnosis of the 
essential pernicious form. Yet megaloblasts have also been 
found in the secondary forms of pernicious anaemia. Among 
the diseases which have given rise to a pernicious type of 
anaemia are syphilis, 25 carcinoma of the stomach, gastric ulcer, 
ulcerating carcinoma of the uterus, hepatic affections, and dis- 
eases of the bone-marrow. 26 Hunter has claimed that the 
condition may be produced by a chronic intoxication from 
oral sepsis, 27 yet this view has not received general accept- 
ance. 28 (It has also been claimed that pernicious anaemia is 
caused by subinfection with intestinal bacteria, and a similar 
condition has been produced in rabbits by injecting them with 
sublethal doses of the colon bacillus. Even the spinal cord 
changes were thus reproduced. 29 — Ed.) Atrophy of the 

25 Muller, Charite-Annalen, vol. xiv. p. 253 ; Klein, Wien. klin. Wochen., 
1891, No. 40. 

29 Literature in Grawitz, p. 231 ; and in Ewing, Clin. Path, of the 
Blood, p. 205. 

"Lancet, 1888, 1889, 1900, 1903. 

28 Bloch, Arch. f. klin. Med., vol. lxxvii. p. 277 ; McCrae, cit. in Ewing, 
p. 211. 

28 Charlton, Jour, of Med. Research, vol. xi., No. 2, 1904. 



THE BLOOD 139 

gastro-intestinal mucous membrane is frequently present in 
pernicious ansemia, but we know that it may also occur without 
causing the disease. Some believe that repeated small hemor- 
rhages may be a causative factor, although this is denied by 
others. It is universally agreed, however, that at least two 
forms of intestinal parasites, bothriocephalus latus and anchy- 
lostoma duodenalis, may produce a pernicious type of ansemia. 
From these numerous observations it has been proved that it 
is impossible to draw any sharp distinguishing line between 
those anaemias of a pernicious type that are due to known 
causes and those that appear to be primary. 

In what manner the various causes affect the blood is not 
always clear. With the possible exception of the anchylos- 
toma duodenale, it seems improbable that losses of blood play 
any great role. In the case of malignant tumors, hsemolytic 
toxins are possibly responsible for the blood condition. 30 It 
seems very probable also that this is the case in the ansemia 
produced by the bothriocephalus latus. 31 Apparently many 
individuals harboring intestinal parasites become immunized 
against their poisons, a supposition which would explain the 
fact that a man may have the parasites in his intestines without 
manifesting any symptoms, and that periods of improvement 
and relapse may alternate. 

The prognosis of the pernicious form of ansemia depends 
mainly upon its cause. In the primary, essential form, the 
outcome is usually fatal; in the secondary forms, recovery 
may take place if the cause be discovered and removed, and 
if the process be not already too far advanced. This is espe- 
cially true of those cases due to intestinal parasites. 

In pernicious ansemia there is unquestionably an increased 
destruction of the red blood-corpuscles, as is proved especially 

so Ktillmann, Ztft. f. Win. Med., vol. v. p. 3. 

"Schaumann and Tallquist, Dcut. med. Wochcnschr., 1898, No. 20; 
Rosenquist, Ztft. f. klin. Med. vol. xlix. p. 193. 



140 CLINICAL PATHOLOGY 

by the abnormal deposits of iron salts in the liver and in other 
organs. The anaemias caused by losses of blood or of serum, 
even though most severe, are unaccompanied by such deposits 
of iron. The pigmentation so frequently found in the spleen, 
the bone-marrow, the kidneys, and the liver, the not infrequent 
jaundice," 2 and increase in the coloring-matter of the urine, 
likewise support the idea that in pernicious anaemia there is an 
unusual destruction of the red blood-corpuscles. 

On the other hand, we have evidence that there is also 
an increased regeneration of erythrocytes, for the red bone- 
marrow spreads to parts of the bones from which it is nor- 
mally absent, and in this red marrow are found erythrocytes 
of various kinds, but more particularly the large nucleated 
variety known as the megaloblasts. By the escape of these 
cells into the blood, one of the most characteristic features of 
pernicious anaemia is produced. 

In pernicious anaemia, therefore, there is both an increased 
destruction and an increased regeneration of red corpuscles, 
but we do not know at present which process is primarily at 
fault. Perhaps the destruction of the erythrocytes is so in- 
tense that even the most marked regeneration does not replace 
the cells destroyed; or perhaps the new cells are so imperfect 
that they cannot resist the normal wear and tear in the body, 
and consequently disintegrate with abnormal ease. Some hold 
that the disease consists essentially in a return to the embryonal 
type of blood formation. 33 Yet there is no reason to con- 
sider that the blood and marrow changes are other than would 
result from an excessively active regeneration of erythrocytes, 
with the escape of immature corpuscles into the circulating 
blood. We do, however, possess direct evidence that the red 
corpuscles of pernicious anaemia are more vulnerable to injury 

32 Sylleba, Cit. in Folia Hsematologica, vol. i. p. 283. 

33 Ehrlich, Kongress f. in. Med., 1892, p. 33 ; Rindfleisch, Virch. Arch., 
vol. cxxi. p. 176; H. F. Muller, Arch. f. klin. Med., vol. li. p. 282. 



THE BLOOD 141 

than are normal corpuscles, and that they may be destroyed 
with comparative ease. 34 This seems to be especially true of 
the malignant anaemia of syphilis. 35 

We know little about the pathological variations in the 
chemical constitution of the red blood-corpuscles, for the neces- 
sary analyses present special difficulties. It is known, however, 
that in cholera the specific gravity of the red cells is increased, 
owing to the loss of water, whereas in other conditions they 
may become swollen from an absorption of water. 

Haemoglobinaemia. — Thus far we have considered the 
haemoglobin only as it constitutes a part of the red blood- 
corpuscles. If it escapes from the corpuscles into the plasma, 
the condition is known as haemoglobinaemia. Haemoglobin 
which has become free in the plasma is quickly removed, prin- 
cipally by the liver, and, to a lesser extent, by the spleen and 
bone-marrow. If these organs fail to remove it completely, 
it is excreted in the urine, giving rise to haemoglobinuria. Ac- 
cording to Ponfick, 30 the latter is produced when about one- 
sixth of the total haemoglobin of the blood is set free from the 
cells. The stromata of the cells which have lost their haemo- 
globin are deposited in the spleen, and cause a swelling of that 
organ. Since the liver manufactures bile-pigments from 
haemoglobin, the bile becomes unusually rich in coloring-matter 
and the faeces become darker. The haemoglobin which is re- 
moved by the liver and kidneys is naturally lost to the body, 
but even that which remains dissolved in the plasma is in 
part rendered useless as an oxygen-carrier by being trans- 
formed into methaemoglobin, a compound, isomeric with oxy- 
hemoglobin, but differing from it, in that it is unable to give 
up its oxygen in the tissues. 

" Pappenheitn, Ztft f. Win. Med., vol. xliii. p. 363; Bloch, Arch. f. 
klin. Med., vol. lxxvii. p. 277. 

" Samberger, Wien. klin. Rundschau, 1003. Nos. 43~45- 
"Virch. Arch., vol. lxii. p. 273, and vol. lxxxviii. p. 445. 



142 CLINICAL PATHOLOGY 

Such a passage of the haemoglobin from the corpuscles into 
the plasma, or, as it is called, a laking of the blood, may be 
brought about by several causes. The stromata of the red 
cells may be directly injured or their osmotic tension may be 
changed so that they become unable to retain their haemo- 
globin; or, on the other hand, a lowering of the osmotic 
pressure of the plasma may bring about the same result. The 
latter seems to be of comparatively little importance, for the 
red cells are normally resistant to considerable changes in the 
osmotic pressure of the plasma, and considerable amounts of 
water may be infused into the circulation without causing a 
laking of the blood. 

We have said that the haemoglobin free in the plasma may 
become converted in part into methaemoglobin. Certain poisons 
possess the property of effecting this conversion of the haemo- 
globin directly within the red cells. If the injury to these 
cells be not too severe, it is possible that the methaemoglobin 
so formed may be transformed back again into oxyhemo- 
globin. 37 If the corpuscles are more seriously damaged, how- 
ever, they disintegrate and their coloring-matter passes into 
solution. 

Three different processes may therefore give rise to haemo- 
globinaemia : first, osmotic changes in the plasma ; secondly, 
a primary injury to the red blood-corpuscles; and thirdly, a 
primary transformation of the oxyhemoglobin into methaemo- 
globin. These processes may run courses quite independently 
of each other, but for the most part, they are combined to 
some extent, and it is often difficult, in the individual case, 
to say which was really the primary change. 

Of the poisons which will give rise to a laking of the blood, 
we may name those of the poisonous fungi, the bile salts, 
arsenuretted hydrogen, and the plasma of alien animals. The 

37 Dittrich, Arch. f. exp. Path., vol. xxix. p. 247. 



THE BLOOD 143 

toxins produced by micro-organisms may also injure the cor- 
puscles, and hasmoglobinaemia has been observed in severe 
cases of typhoid fever, scarlet fever, and other infectious 
processes, it being especially severe in certain forms of tropical 
malaria (fievre bilieuse hemoglobinurique). In such cases, 
the plasma dissolves its own corpuscles. Italian observers 38 
have described such a globulicidal action of the plasma in 
association with a great variety of diseases. Whenever the 
destruction of the corpuscles exceeds a certain limit, hsemo- 
globinsemia and, ultimately, hemoglobinuria occur. 

The Haemolytic Action of Alien Plasmas. — The whole 
subject of the destruction of red blood-corpuscles, especially 
by alien blood, has in recent years become a matter of very 
great interest on account of the broad biological principles 
involved. It has long been known that the blood of certain 
animals has the property of destroying the corpuscles of other 
animals. For this reason the transfusion of blood from one 
animal into another has failed of any practical application. 
The red blood-corpuscles of certain animals are peculiarly sus- 
ceptible to such changes of environment, while the sera of 
others are especially poisonous. A schematic arrangement of 
the bloods of various animals according to these properties 
is, however, hardly possible on account of the great individual 
variations. The serum of an animal may even dissolve the 
red blood-corpuscles of another individual of the same species. 39 
According to some writers, the haemolysis is due to the dif- 
ferent osmotic properties of the foreign serum ; but at present, 
most investigators believe that the haemolysis is produced by 
certain chemical substances in the foreign serum, which have 
been designated by Buchner and by the French school as alex- 
ins, by Ehrlich and his pupils as complements (addiments). 

18 Maragliano, Kongr. f. in. Med., 1892, p. 152; Maragliano and Castel- 
lino, Ztft. f. klin. Med., vol. xxi. p. 415. 

"Ehrlich and Morgenroth, Berl. klin. Wochenschr., 1900, No. 21. 



144 CLINICAL PATHOLOGY 

These alexins are destroyed if they are heated to a temperature 
of about 56 C. for half an hour. 

It is possible to increase the hemolytic action of a serum 
enormously. If the red corpuscles of an animal A, be in- 
jected into an animal B, then the serum of B usually acquires 
the property of destroying the corpuscles of A, even though 
it had not possessed this property previously, and if it had had 
the property before, its hsemolytic power may be increased 
many times by this treatment. The same results are obtained 
if, instead of the entire red corpuscles, the stromata alone 
are used. This process is spoken of as an immunization of 
one animal against the red blood-corpuscles of another; and 
it is analogous to a form of immunity which follows similar 
injections of bacteria into the animal body (bactericidal im- 
munity). 

To what substances does the serum owe its increased 
hsemolytic activity? Let us describe the classical experiment 
of Bordet. The blood-serum of a normal rabbit does not dis- 
solve the red blood-corpuscles of the guinea-pig; yet several 
intraperitoneal injections of guinea-pig's blood confer upon 
the rabbit's serum the property of dissolving the guinea-pig's 
erythrocytes with great rapidity. This property is, however, 
lost if the immunized rabbit's serum be heated to 56 C. for 
half an hour. Yet this serum, thus inactivated by heat, regains 
its activity if fresh normal rabbit's serum, itself inactive, be 
added to it. Two substances, therefore, must take part in an 
haemolysis of this character : the one is contained in normal 
serum and is destroyed by a temperature of 56 C. ; the other 
is formed in the process of immunization and is resistant to 
such a temperature. The former is the alexin of which we 
have already spoken. The latter, the so-called immune body, 
is specific for the kind of blood injected. There is a great 
affinity between it and the corresponding corpuscles, so that 
if the inactivated serum and the foreign red corpuscles be 



THE BLOOD 145 

mixed and allowed to stand, and if then the red cells be 
separated by centrifugalization, they will carry the immune 
body out of the serum with them, and they are then susceptible 
to the action of fresh normal serum which would otherwise 
be without effect upon them. 

It cannot be doubted that the haemolysis induced by im- 
mune sera is due to the action of these two substances. All 
are not yet agreed, however, as to whether the haemolysis pro- 
duced by the action of normal sera is likewise due to two sub- 
stances or is due only to one. Personally, I believe that the 
former supposition is supported by the better evidence. Thus 
the inactivated serum of a dog will not dissolve the red blood- 
corpuscles of the guinea-pig, but it is able to do so if fresh 
guinea-pig's serum be added, although the latter alone is 
naturally without any action upon its own corpuscles. It is 
difficult to explain this fact other than by supposing that 
there are two substances involved in the process ; the immune 
body being contained in the dog's serum, the complement in 
that of the guinea-pig. 

Ehrlich has brought forward a great array of facts in 
support of the view that there are in normal, as well as in 
immune, sera a great variety of immune bodies and of com- 
plements. The question is one of considerable importance in 
bacteriology and the theory of immunity, and will be con- 
sidered in another place. 

Paroxysmal Hemoglobinuria. — The condition known as 
paroxysmal haemoglobinuria is characterized by the passage of 
red to dark-brown urine. Such urine contains some of the 
more usual forms of albumin, but its characteristic color is 
due to the presence of free oxyhemoglobin and methaemo- 
globin with few if any red blood-corpuscles, in the typical 
cases. The paroxysm is usually accompanied by chills, fever, 
and pains in various parts of the body. As a rule, the liver 
and spleen become enlarged, and jaundice may develop. After 



146 CLINICAL PATHOLOGY 

a few hours or days, the symptoms disappear, and only the 
dark-colored faeces remain as evidence of the paroxysm which 
has just ceased. 

Malaria and syphilis appear to be predisposing causes of 
this disease. In some individuals the attack is precipitated by 
muscular exertion, in others by exposure to cold. Indeed, 
some patients void the characteristic urine whenever they are 
exposed to a low temperature, or even when a single hand is 
dipped into ice-water. During the intervals between the par- 
oxysms, the patient may appear to be perfectly well, or he 
may continue to show albumin in the urine. Ralfe 40 has 
reported the case of a man who had cyclic albuminuria in con- 
junction with paroxysmal hemoglobinuria, and a similar case 
has been observed by the author. 

A hcemoglobinaemia probably antedates, in all cases, the 
appearance of the blood-pigments in the urine. In these 
patients, the red blood-corpuscles appear to be less resistant 
than normal, so that they more readily succumb to unfavorable 
influences. The nature of these unfavorable influences has 
been a matter of dispute. Some have held that the cold itself 
is the destructive agent, but careful direct observations have 
failed to confirm this view. The red corpuscles of these 
individuals are no more readily destroyed by cold than are 
those of normal persons. 41 Chvostek believes that the cold 
causes a stasis of the blood in the internal organs, and that 
this leads to the destruction of the red cells; yet it is difficult 
to see why there should be any stasis of blood in the internal 
organs, and the question remains sub judice. Undoubtedly 
vasomotor phenomena, induced by cold, initiate many of the 
paroxysms, and quite probably the red blood-corpuscles are 
destroyed because they possess less resistance than normal 

"Lancet, 1886, p. 764. 

41 Ehrlich, Charite-Annalen, vol. x. p. 142 ; Chvostek, Ueber das Wesen 
der paroxysmal Hemoglobinuria, Leipzig, 1894. 



THE BLOOD 147 

cells. 42 It is possible that the circulatory disturbances are in 
some way directly responsible for the destruction of the red 
corpuscles. 

The large quantity of blood-pigment liberated from the 
corpuscles is partially taken up by the liver, the disintegrated 
stromata are deposited in the spleen, and both of these organs 
become enlarged. The haemoglobin that remains in the plasma 
is excreted by the kidneys, and seems to injure them, for a 
certain amount of albumin likewise passes through into the 
urine. The haemoglobin taken up by the liver is mostly con- 
verted into the bile-pigments, and for this reason the stools 
become dark. The fever, anxiety, and occasional dilatation 
of the heart may quite possibly be due to the toxic properties 
of substances resulting from the disintegration of the stromata 
of the affected corpuscles. 43 

Other Causes which injure the Red Blood-Corpuscles. — 
Extensive superficial burns may cause the red corpuscles to 
break up into smaller particles, and lead to a liberation of 
haemoglobin in the plasma, not only from these disintegrated 
corpuscles but from others, which, microscopically at least, 
appear to be normal. 44 The haemoglobin, dissolved in the 
plasma, is taken up by the liver and kidneys, partly as methae- 
moglobin, and the urine consequently contains both these pig- 
ments. The cellular residues are taken up especially by the 
spleen and bone-marrow, and, to a lesser extent, by other 
organs. They produce symptoms which will be described 
later. 

Many poisons are able to convert the haemoglobin of the 
red blood-corpuscles into methaemoglobin, among the more 
important of which are potassium chlorate, acetanilide, and 

"Kretz, Wien. klin. Wochenschr., 1903, No. 18; Donath, Ztft. f. klin. 
Med., vol. lii. p. i. 

" Stadelmann, Der Ikterus, Stuttgart, 1891. 

"Silbermann, Virch. Arch., vol. cxix. p. 488; Wilms, Mitth. a. d. 
Grenzgeb., vol. viii. p. 393. 



148 CLINICAL PATHOLOGY 

other coal-tar products. 45 The first does not exert the same 
action upon the blood of all species of animals, for the cor- 
puscles of some appear to be especially resistant to the action 
of this poison. 46 Even in the same individual, accessory causes 
may render the corpuscles more or less vulnerable to the 
action of potassium chlorate. Thus Mering 4T has shown that 
the red cells are rendered susceptible by fever or by a reduc- 
tion in the normal alkalinity of the blood, produced by the 
administration of mineral acids. The toxic effects from the 
administration of potassium chlorate appear, therefore, to de- 
pend upon two factors, — first, upon the amount of the salt in 
the blood at a given time; and secondly, upon the resistance 
possessed by the red corpuscles. 

Systemic Effects resulting from the Rapid Destruction 
of Red Blood-Corpuscles. — The effects of such intoxications 
upon the body as a whole depend partly upon the loss of func- 
tioning haemoglobin and partly upon the toxic substances de- 
rived from the destroyed corpuscles. In very severe intoxica- 
tions with potassium chlorate, death results from the diminution 
in the respiratory capacity of the blood, caused by the loss of 
haemoglobin. 

The destruction of a large number of red corpuscles sets 
free in the plasma certain substances, apparently enzymes, 
which tend to produce intravascular clotting. A limited quan- 
tity of such substances may be neutralized or destroyed by 
the living organism; but when they appear in very large 
amounts, they give rise to thrombi in the smaller blood-vessels. 
As results of such thrombi, we find necroses in various tissues, 
and the gravity of the intoxication often depends upon the 
localities in which the coagula form. 

"Marchand, Arch. f. exp. Path., vol. xxii. pp. 23, 201, 273, 347; F. 
Muller, Deut. med. Wochens., 1887, No. 2. 

49 v. Limbeck, Arch. f. exp. Path., vol. xxvi. p. 39. 
" Mering, Das chlorsaure Kali, Berlin, 1885. 



THE BLOOD 149 

The fact that there is a slow coagulation of the blood 
in certain cases of extensive burns in no way excludes the 
possibility that thrombi have formed, for we know that the 
presence of substances in the blood which favor coagulation 
may in turn give rise to substances having the very opposite 
effect, so that ultimately the coagulation will be retarded. 
Opinions differ as to the role played by these thrombi in the 
above-mentioned intoxications and burns. Some observers 
have found them in the majority of cases, 48 while others have 
missed them with equal frequency. 49 

The large quantities of haemoglobin or methsemoglobin 
which may pass into the urine in these conditions seem to 
injure the kidneys directly, and not infrequently the urine 
contains large amounts of albumin, numerous blood and epi- 
thelial cells, and a great variety of casts, the most charac- 
teristic of which are composed of clumps of blood-pigment. 
The quantity of urine may diminish up to complete anuria, 
and the patient may die of uraemia. The danger from renal 
complications persists for some time after the original cause 
of the haemoglobinaemia has disappeared. 

THE WHITE BLOOD-CORPUSCLES. 

The white blood-corpuscles may be divided into groups 
according to their size, the character of their nuclei, and the 
staining reactions of their protoplasm. About seventy per 
cent, are made up of cells that are slightly larger than red 
corpuscles, and that contain irregular nuclei and protoplas- 
mic granules, staining with neutral aniline stains. From 
twenty-five to twenty-eight per cent, arc made up of mono- 
nuclear cells, from two to four per cent, of which are quite 

" Silbermann, Virch. Arch., vol. cxvii. p. 228, and vol. cxix. p. 488; 
Welti, Zicg. Bcitrag., vol. iv. p. 519. 

*' Falkenberg, Diss. Marburg, 1890; Wilms, Grcnzgcb., vol. viii. p. 
393; Bardecn, Johns Hopkins Hosp. Reports, vol. vii. 



150 CLINICAL PATHOLOGY 

large, whereas the remainder are about the size of red 
blood-corpuscles. In addition to these cells, there are from 
one to four per cent, of eosinophiles, characterized by the 
presence of large acid-staining granules in their protoplasm, 
and from 0.5 to two per cent, of cells containing large irregu- 
lar basic granules (the mast-cells). 

The origin of the various forms of leucocytes is still un- 
settled. According to Ehrliclvs well-known views, the small 
mononuclear forms are derived from the lymphoid tissues of 
the body, while the polymorphonuclear neurophilic leucocytes 
are derived from certain large mononuclear cells in the bone- 
marrow. We hold, however, with those who believe that 
no such sharp distinction can be made between these two 
varieties of cells. 50 

Physiological Leucocytoses. — The number of leucocytes 
in a cubic millimetre of blood is normally about eight thou- 
sand. Children have, on the average, somewhat more, — about 
nine thousand ; weak and poorly nourished persons, somewhat 
less. The number of leucocytes in the peripheral blood varies 
even in the same individual at different times. Thus it is 
usually increased after a meal, especially when the meal consists 
largely of proteid material. 51 Such a " digestion leucocytosis" 
is absent in some individuals normally, but it is especially 
apt to be absent in certain diseases, above all in carcinoma of 
the stomach. During pregnancy, more particularly in the 
later months, the number of leucocytes is increased. A leuco- 
cytosis is also physiological in the new-born. Cold baths and 
exercise likewise increase the number of leucocytes in the 
peripheral blood. 52 Some regard this latter as an effect of the 

50 Grawitz, Path, des Blutes ; Lowit, Kongress f. in. Med., 1899 ; 
Pappenheim, Virch. Arch., vol. clvii. p. 54; vol. clix. p. 40; vol. clxiv. p. 

374 

51 Pohl, Arch. f. exp. Path., vol. xxv. p. 31. 

53 Schulz, Arch. f. klin. Med., vol. li. p. 249 ; Thayer, Johns Hopkins 
Hosp. Bull., April, 1893. 






THE BLOOD 151 

more rapid blood-current which tears the leucocytes away from 
the vessel walls of the internal organs and throws them into 
the general circulation, and especially into the peripheral 
capillaries from which the samples of blood are taken. 

The conditions which we have just been describing have 
been termed physiological leucocytoses. The increase in the 
number of white cells does not usually exceed thirty per cent, 
of the normal, although in children the number may be 
doubled. The proportion between the mononuclear and the 
polynuclear cells remains unchanged in this form of leuco- 
cytosis. Since the counts are made from the blood of the 
peripheral capillaries, the question arises, Is there an actual 
increase in the total number of leucocytes in the blood, or is 
there merely a redistribution of the cells, more going to the 
periphery and fewer remaining in the interior of the body? 
Studies on animals have shown that there is normally a greater 
number of leucocytes at the periphery than in the internal 
organs, but that during the digestion leucocytosis, at least, the 
number in both places is increased. 53 The new cells are prob- 
ably derived from the lymph and from the various organs of 
the body, for no signs of an active regeneration of these cells are 
to be found. The digestion leucocytosis appears to be due to 
the presence of substances in the blood which attract the leuco- 
cytes. Such substances appear to be present in largest amounts 
after the ingestion of proteid food, but not all varieties of 
proteid food exert the same influence. Indeed, it is uncertain 
just which products of digestion are responsible for the normal 
digestion leucocytosis. Possibly this leucocytosis indicates a 
transportation of proteid material from the intestines to other 
parts of the body. 

A hyperleucocytosis is frequently but not always preceded 
by a hypoleucocytosis. Lowit 54 interpreted this as a primary 

53 Goldscheider and Jacob, Ztft. f. klin. Med., vol. xxv. p. 403. 
M Studien 7.. Physiol, des Blutcs, etc., Jena, 1892. 



152 CLINICAL PATHOLOGY 

destruction of the white corpuscles which precedes a regenera- 
tion. Goldscheider and Jacob 55 and others, 56 on the other 
hand, failed to find any sign of destruction, and believe that 
this hypoleucocytosis is caused by a massing of the leucocytes 
in the capillaries of the lungs. More work is necessary to 
decide this question. 

Pathological Leucocytoses — Many infections cause an 
increase in the number of white blood-corpuscles in the 
peripheral blood, the so-called pathological leucocytosis. Al- 
though the same varieties of leucocytes are present as in health, 
the relative proportions are usually changed. In the more 
common form of pathological leucocytosis, the percentage of 
lymphocytes is diminished, whereas that of the polymorpho- 
nuclear neutrophiles is increased, from eighty-eight to ninety- 
five per cent, of the latter being frequently found, in contrast 
to the normal of seventy to eighty per cent. 

In other forms of pathological leucocytosis, the relative 
number of the lymphocytes is increased, 57 such a blood-picture 
being presented by many cases of pertussis. Of especial in- 
terest would be the investigation of the blood-changes in those 
diseases which give rise to exudates rich in lymphocytes, such 
as tuberculous meningitis, pleurisy, etc. ( Such cases have been 
investigated by Fauconnet, who failed to find a lymphocytosis 
in most cases. 58 — Ed.) 

Still another form of leucocytosis is characterized by the 
relative increase in the eosinophilic white blood-corpuscles. 
This has been observed in bronchial asthma, trichinosis, and a 
variety of other diseases. 

Pathological leucocytosis of the first type occurs especially 
as the result of inflammatory processes and, above all, in 

"Loc. cit. 

M Ewing, New York Med. Jour., March 2, 1895. 

"Minkowski, Kongr. f. in. Med., 1899, p. 179; H. Strauss, Charite- 
Annalen, vol. xxiii. 

"Arch. f. klin. Med., vol. lxxxii., Nos. 1 and 2. 



THE BLOOD 153 

association with those which are accompanied by a purulent 
exudation, although exudation is not a necessary concomitant. 
In certain infectious diseases — e.g., typhoid fever, malaria, 
and uncomplicated tuberculosis — there is usually no increase 
in the number of white blood-corpuscles in the circulating 
blood. 

The infectious leucocytoses are probably caused either by 
the secretions of the living bacteria or by the disintegrated 
bodies of dead ones. Experimentally, it has been shown that 
various constituents of the bacterial cell may exert an attrac- 
tive influence upon the leucocytes (positive chemotaxis). 
Many other substances also appear to exert such a chemo- 
tactic influence, and the same substance may, under one set 
of circumstances, attract the leucocytes, and under another, 
repel them. The origin of the extra leucocytes has not yet 
been definitely settled, and we do not know whether they are 
derived from the bone-marrow, the lymph-glands, or possibly 
from other tissues. 

Whether or not a pathological leucocytosis is of advantage 
to the individual suffering from an infectious disease is a 
matter of great importance. Evidence is constantly being 
accumulated in support of the view that the increased number 
of leucocytes is beneficial, and assists the organism in warding 
off the dangers of the infection. 59 The importance of the 
subject certainly merits further study. 

Leucocytoses of the neutrophilic type may also result from 
hemorrhage and from malignant cachexias. The latter, how- 
ever, do not always cause an increase in the number of leuco- 
cytes in the peripheral blood, and we do not know what is the 
determining factor in the individual case. Grawitz 60 found 
that after injecting carcinomatous material into an animal's 
blood, the latter became more dilute and the number of leuco- 

" Jakob, Kongress f. in. Med., 1897, p. 395. 
80 Deut. med. Wochenschr., 1893, No. 51. 



154 CLINICAL PATHOLOGY 

cytes was frequently increased. These changes were believed 
to result from an increased flow of lymph into the blood, and 
possibly such an increased flow of lymph is the explanation 
not only of these leucocytoses due to malignant disease, but 
of those others which follow acute hemorrhage. (If this ex- 
planation were correct, we should expect to find a relative 
lymphocytosis, yet such is not found. — Ed.) 

Leucocytoses, in which the eosinophilic cells are increased, 
occur in a variety of diseases, of which we may mention bron- 
chial asthma, various cutaneous lesions, trichinosis, and in- 
fections with intestinal parasites. It is interesting that in 
most of these diseases there exists a local collection of eosino- 
philic cells at the main seat of the disease ; for example, in the 
bronchi and in the exudate of bronchial asthma, in the lesions 
of certain skin affections, 61 and about the embryos in trichi- 
nosis. 62 

The number of white cells in the blood in pathological leu- 
cocytoses usually ranges between ten thousand and thirty thou- 
sand per cubic millimetre, but the number may reach one 
hundred and sixty-eight thousand (Grawitz). 

Leucopenia. — A diminution in the number of leucocytes 
in the peripheral blood, a leucopenia, occurs in a variety of 
diseases. It has been observed in cachexias, intoxications, 
many anaemias, and in some infectious diseases, notably in 
typhoid fever and malaria. 63 

In such leucopenias, the proportion between the numbers 
of the various kinds of white cells is usually changed. For 
example, in typhoid fever there is a relative increase in the 
number of lymphocytes. The cause of these leucopenias is 
unknown. Possibly they are due to a negative chemotaxis, or 

" Bettmann, Munch, med. Wochenschr., 1898, No. 39. 

62 Brown, Jour, of Exp. Med., May, 1898. 

63 Thayer, Johns Hopkins Hosp. Reports, vol. iv., No. 1 ; Billings, 
Johns Hopkins Hosp. Bull., October, 1894. 



THE BLOOD 155 

possibly to some lesion of the sites of origin of the leuco- 
cytes. 

Leukaemia and Pseudoleukaemia. — The disease pseudo- 
leukaemia, or Hodgkin's disease, is characterized by an en- 
largement of the lymph-glands and by an increase of the 
lymphatic tissues throughout the body. Clinically it is some- 
times difficult to distinguish this disease, on the one hand, 
from generalized glandular tuberculosis, and, on the other, 
from lymphosarcoma. Anatomical investigations have shown, 
however, that the three diseases are quite distinct. 04 

The number of leucocytes in the peripheral circulation in 
pseudoleukaemia is usually either normal or subnormal, but, 
as a rule, an increase in the relative number of the mononuclear 
forms is present. Although these blood-findings do not differ 
essentially from those of glandular tuberculosis, they serve 
to establish a fairly sharp line between pseudoleukaemia and 
typical lymphatic leukaemia. 

The true leukaemias are characterized by an enormous in- 
crease in the number of leucocytes and by characteristic 
changes in the forms and relative numbers of those present. 
The number of white cells in the blood varies from fifty 
thousand to two hundred thousand per cubic millimetre in 
cases of moderate severity. Even one million and over have 
been observed in the peripheral circulation, but it is doubtful 
if in these patients the number throughout the body is pro- 
portionately high. 

Several forms of leukaemia are recognized, the division 
being based upon the changes in blood-forming organs and the 
varieties of cells in the blood. In the first place, we have mye- 
logenous leukaemia, which is characterized by the presence of 
large numbers of so-called neutrophilic myelocytes, which 

** Reed, Johns Hopkins Hosp. Reports, vol. x., Nos. 3-5 ; Longcope, 
Bull, of the Ayer Clin. Lab., No. 1 ; Simmons, Jour, of Med. Research, 
vol. ix. 



156 CLINICAL PATHOLOGY 

usually make up from twenty to sixty per cent, of the total 
number of leucocytes. These myelocytes are large mono- 
nuclear cells, containing- neutrophilic protoplasmic granules. 
They are not in themselves absolutely pathognomonic of 
myelogenous leukaemia, for they may be found in small num- 
bers in other conditions, such as infectious diseases and severe 
anaemias; yet here their number never reaches the proportion 
which is characteristic of myelogenous leukaemia. (In bone- 
tumors, however, from four to seventeen per cent, of myelo- 
cytes may be found. 65 — Ed.) 

The second form of leukaemia is characterized by an 
enormous increase in the number of the small mononuclear 
leucocytes, which usually make up from eighty to ninety-eight 
per cent, of all the white blood-corpuscles. 

In either of these forms of leukaemia, the total number of 
leucocytes may be reduced by various causes, among which 
may be named acute septic infections, pneumonia, tuberculosis, 
etc. (Similar reductions have followed exposures to the ac- 
tion of the X-ray. 66 In some instances, these reductions in the 
total number of leucocytes have not materially affected the 
differential count, characteristic of the form of leukaemia under 
consideration ; so that the latter would still enable one to sus- 
pect the true condition. In other instances the blood has be- 
come, to all appearances, absolutely normal. Nevertheless it 
is very doubtful if these reductions are anything more than 
remissions in the course of the disease, for sooner or later, in 
most cases, a relapse has occurred. — Ed.) 

A third form of leukaemia has been described, the so-called 
acute leukaemia. Typical cases of this form are characterized 
by the presence in the blood of numerous, large, mononuclear, 
non-granular cells, which have been regarded by some authors 

"Kurpjuwert, Centr. f. in. Med., 1904, No. 15. 

86 Dock, Am. Med., December 24, 1904 ; Schirmer, Zentralbl. f. Grenz- 
geb, vol. vii., No. 1. 



THE BLOOD 157 

as large lymphocytes. 67 Leukaemia running an acute course 
may, however, present the blood-picture of myelogenous leu- 
kaemia, 68 and some incline to regard the large mononuclear 
cells above described as myelocytes without neutrophilic granu- 
lations. 69 

Most patients with leukaemia show an associated anaemia. 
Poikilocytosis may be present, and in no other condition do 
we see nucleated red cells in such numbers as in some cases 
of leukaemia. These changes in the red blood-corpuscles de- 
pend upon alterations in the bone-marrow, which are probably 
present in every case of leukaemia. 

The blood-serum in leukaemia sometimes contains proteids 
not normally present. Neucleo-albumins and deutero-albu- 
moses have been found, 70 but at present the meaning of these 
findings is not clear. Charcot-Leyden crystals have been found 
in lymphatic leukaemia in the blood as well as in the fluids 
of the spleen. These crystals appear to bear some relation to 
the presence of eosinophilic cells. 

Leukaemia is a disease of middle life, but it may occur 
in the aged as well as in the very young. It leads, almost 
without exception, to a fatal termination. At autopsy the 
bone-marrow is found to have lost its ordinary fatty char- 
acter, and to consist of reddish or grayish tissue. Histologi- 
cally this consists mainly of the varieties of cells found in the 
circulating blood, or of their progenitors. Thus in lymphatic 
leukaemia, the mononuclear cells in the marrow are enor- 
mously increased, whereas in myelogenous leukaemia, the 
increase is principally in the myelocytes. In the later stages 
of leukaemia, changes in the marrow develop which indicate 

87 Fraenkel, Deut. nied. Wochcns., 1895, p. 639. 

** Billings and Capp, Am. Jour, of the Med. Sci., September, 1903. 

" Askanazy, Virch. Arch., vol. cxxxvii. p. 1; Ewing, Clin. Path, of 
the Blood, 1903, p. 245. 

"Matthes, Berl. klin. Wochens., 1894, Nos. 23, 24; Erben, Ztft. £. 
Hcilk., vol. xxiv. ; Schrumm, Hofmeister's Beitr., vol. iv. p. 442. 



158 CLINICAL PATHOLOGY 

a rapid multiplication of those cells which give rise to the 
red blood-corpuscles, and correspondingly the number of 
nucleated red cells in the circulating blood is increased. 

The liver and spleen are enlarged, partly because of the 
accumulation of leucocytes in these organs, and partly because, 
in lymphatic leukaemia at least, there is a proliferation of 
the lymphoid cells in situ. In various other parts of the 
body, leukemic deposits may also occur, probably owing to a 
primary formation of white cell thrombi with secondary multi- 
plication of the cells so deposited. 

Most leukaemias run a chronic course. The acute form is 
characterized clinically by fever, hemorrhages, and a rapidly 
fatal outcome, thus presenting the picture of an acute infec- 
tious disease. As we have already said, the blood in many 
cases, but not in all, is quite characteristic. 71 In chronic leu- 
kaemia, hemorrhages and fever may also occur, but they are 
relatively less frequent. Both symptoms are of interest, for 
it is possible that they are caused by a destruction of blood- 
corpuscles. Fever may also occur in pseudoleukaemia, and at 
times it assumes a characteristic relapsing character, with 
periods of apyrexia. 72 

The chief feature differentiating pseudoleukaemia from the 
ordinary type of leukaemias is the number of leucocytes in the 
unit-volume of blood. The former begins in the lymphatic 
glands, whereas in the latter the bone-marrow is constantly, 
and perhaps primarily, affected. A conversion of a pseudo- 
leukaemia into a true lymphatic leukaemia is very rare, although 
a few such cases have been reported. In one of these, 73 a 
rupture of the hyperplastic tissue of a pseudoleukaemic gland 

71 Hamman, Am. Med., vol. viii. p. 138. 

72 Pel, Berl. klin. Wochenschr., 1885, No. 1, and 1887, No. 35; Ebstein, 
Berl. klin. Wochenschr., 1887, Nos. 31 and 45 ; Westphal, Arch. f. klin. 
Med., vol. li. p. 103. 

73 Claus, Ueber das maligne Lymphom. Diss., Marburg, 1888. 



THE BLOOD 159 

into a vein could be directly demonstrated, and coincidently 
a lymphatic leukaemia developed. 

The abnormal leukaemic cells may reach the blood either 
by being passively washed into it, or by their active amoeboid 
movements. Ehrlich has maintained that the former occurs 
in the lymphatic form of the disease and the latter in the 
myelogenous form. With our present knowledge, however, 
it seems impossible to maintain this distinction. 74 

What relation do the changes in the spleen, the bone- 
marrow, and the lymphatic apparatus bear to each other, and 
what relation do they bear to the diseases under consideration ? 
In every case of leukaemia, probably, the bone-marrow is more 
or less affected, although the changes may be only micro- 
scopical, 75 and in some instances it is the only tissue which 
presents important pathological alterations. 76 It seems quite 
certain that the bone-marrow is always primarily affected in 
myelogenous leukaemia, whereas the lymphatic tissues of the 
body are primarily affected in lymphatic leukaemia and in 
pseudoleukemia. In lymphatic leukaemia the lymphatic tissues 
of the lymph-glands, the spleen, the intestine, or of the bone- 
marrow are increased. Whether the lymphocytes present in 
the blood originate solely from the bone-marrow, 77 or whether 
they originate from the various collections of lymphoid cells 
throughout the body, is not yet definitely known. It is, how- 
ever, of considerable interest that instances of lymphatic leu- 
kaemia without enlargement of the lymph-glands have been 
reported. 78 Such cases demonstrate how careful we must be 

71 Lowit, Kongr. f. in. Med., 1889, p. 139. 

"Dennig, Munch, med. Wochcnschr., 1901, No. 4; Blumer and Gordi- 
nier, Medical News, 1903. 

70 Littem, Berl. klin. Wochcnschr., 1877, Nos. 19, 20; Litten, Kongr. f. 
in. Med., 1892, p. 159. 

77 Pappcnheim, Ztft. f. klin. Med., vol. xxxix. p. 171; in opposition, 
see Rosenfeld, Ztft. f. klin. Med., vol. xlii. p. 117. 

" Pappcnheim, loc. cit. ; Blumer and Gordinicr, loc. cit. 



160 CLINICAL PATHOLOGY 

not to assume that lymphatic leukaemia is essentially a disease 
of the lymphatic glands. It seems more probable, indeed, that 
it is primarily a disease of the lymphoid tissue of the bone- 
marrow, though recent work has shown that numerous mitoses 
may be present in other organs, 79 and it is quite possible that 
white corpuscles may arise in tissues which normally produced 
these cells only during embryonal life, as, for example, in the 
liver. 

In regard to the nature of the pathological process in 
leukaemia, we wish again to recall the observation from 
Marchand's laboratory on a case of lymphatic leukaemia which 
apparently originated from the rupture of a hyperplastic 
lymphatic gland into a vein. so Many facts favor the view 
that a growth of cells into the blood-stream is the cause of 
the blood-changes in leukaemia. Thus, as illustrated, pseudo- 
leukaemia may change into a true leukaemia by the rupture of 
a hyperplastic gland into the circulation. The hyperplasias 
of the lymphoid and myeloid tissues are regarded by some 
authors as analogies of tumors, 81 and when this tumor tissue 
escapes into the blood-current leukaemia results. Since the 
conditions in the bone-marrow especially favor such a rupture 
into the blood-stream, pathological changes in this tissue are 
most apt to give rise to leukaemia. 

(" Aleukaemic Leukaemia." — Within recent years evidence 
has accumulated which demonstrates that we cannot rely en- 
tirely upon the blood-findings in making a diagnosis of leu- 
kaemia, but that the pathological changes in the tissues is of 
even greater importance. We have already stated that under 

79 Askanazy, Virch. Arch., vol. cxxxvii. p. I ; Gumprecht, Arch. f. klin. 
Med., vol. lvii. p. 523; H. F. Miiller, Zentralbl f. Path., vol. v. pp. 553, 
601 ; etc. 

80 Claus, loc. cit. 

81 Pappenheim, Ztft. f. klin. Med., vol. Hi. p. 285 ; Banti, Ztrbl. f. Path, 
vol. xv. p. 1; Sternberg, Verhandl. d. path. Gesellsch., 1903, p. 30; 
Warthin, Trans. Assoc, of Am. Physicians, 1904. 



THE BLOOD 161 

the influence of acute infectious diseases, X-ray treatment, etc., 
the characteristic blood-picture of leukaemia may become modi- 
fied so that it is absolutely impossible to detect any alterations 
in the blood ; yet, from the fact that these cases usually again 
relapse, we may infer that the disease has not disappeared. 
Certain cases of profound anaemia, with no absolute increase, 
or even with a diminution in the total number of the leuco- 
cytes, have shown at autopsy the characteristic qualitative 
changes of a lymphatic leukaemia. From the pathological 
picture presented, these must be regarded as instances of leu- 
kaemia, in which characteristic leukaemic changes did not 
appear in the blood; i.e., they are aleukaemic leukaemias. 82 

The pathological picture presented by these cases differs 
entirely from that described by Reed and others as character- 
istic of Hodgkin's disease, and the recognition of this masked 
form of leukaemia throws very grave doubt upon the reported 
cases in which Hodgkin's disease was believed to have be- 
come converted into leukaemia. It seems very probable that 
all these were instances of leukaemia in which the blood- 
changes were first absent and later present. It is difficult to 
see how the glands of Hodgkin's disease should become leu- 
kaemic, for they possess none of the ordinary microscopical 
characteristics of leukaemia. It is doubtful if Hodgkin's dis- 
ease can be distinguished from aleukaemic leukaemia without 
microscopical examination of the lymphatic glands, though 
possibly a relative increase in the mononuclear leucocytes of 
the blood will prove to be characteristic of aleukaemic lym- 
phatic leukaemia. — Ed. ) 

The theory that leukaemia is due, not to an excessive pro- 
duction, but to a diminished destruction of the leucocytes, 
deserves to be considered merely to be condemned, for it has 
been proved that the destruction of these cells, far from being 
decreased, is actually increased. Many leucocytes may be seen 

" Blumer, Albany Med. Annals, April, 1905. 

1 1 



162 CLINICAL PATHOLOGY 

in blood-preparations in various stages of degeneration, and 
the increased elimination of uric acid and of the xanthin bases 
through the urine indicates an increased destruction of the 
nucleo-proteids of the body, which are derived, in all proba- 
bility, from the nuclei of the leucocytes. 

The final cause of leukaemia is still unknown. Lowit 
believes that it is due to an infection with sporozoa, and he 
has described a separate parasite for each form of leukaemia. 83 
Yet his view has not received general acceptance. 84 

PLASMA AND SERUM. THE TOTAL QUALITY OF BLOOD. 

Little is known about pure plasma, principally because it 
is so difficult to preserve it without coagulation. The serum, 
resulting from coagulation, differs from the plasma within 
the blood-vessels, in that it contains no fibrinogen, but does 
contain fibringlobulin and the fibrin ferment. Probably other 
changes, at present but little understood, also take place in 
the proteids of the blood during coagulation. 

The Quantity of Fibrin — When normal blood coagulates, 
about o.i to 0.4 per cent, of its weight separates as fibrin. 
This may be pathologically increased up to one to 1.3 per 
cent., an increase which is seen especially in diseases accom- 
panied by inflammatory exudations, such as pneumonia, pleu- 
risy, and acute articular rheumatism. In other conditions, 
the yield of fibrin is less than 0.1 per cent., notably in the 
anaemias, typhoid fever, and septicaemia. There exists a cer- 
tain parallelism between the number of leucocytes and the 
amount of fibrin present in the blood, but the parallelism is by 
no means a strict one. 85 

Our knowledge of the physiology of blood-coagulation is 
still so limited that it would be hazardous to speculate on the 

83 Kongr. f. in. Med., 1900, p. 322. 

84 Turk, Kongr. f. in Med., 1900, p. 251. 

85 Moll, Wien. klin. Wochens., 1903, No. 44. 



THE BLOOD 163 

significance of pathological variations in the amount of fibrin 
in the blood and the effect that these variations have upon 
coagulation. It has been assumed that if the amount of 
fibrin be diminished, the blood will coagulate slowly and 
there will be a tendency to hemorrhages, whereas, if the 
amount be increased, coagulation will be rapid and there will 
be a tendency to thrombosis. These assumptions, however, 
are not sufficiently supported by facts. 

The Blood-Serum. — All substances formed in the meta- 
bolic processes within the body and all food-stuffs introduced 
from without pass through the blood; although they may be 
present there only in minute traces, because they are so quickly 
removed by the various organs. It would be impossible to 
discuss in this place all those conditions in which some con- 
stituent or other of the serum is changed, as happens, for 
example, in diabetes, and it seems better to reserve such a dis- 
cussion for the chapters on metabolic disorders. 

One substance, however, may be mentioned in this con- 
nection, — viz., fat. Fatty substances are constantly present in 
the blood, 86 the amount being increased during the digestion 
of meals containing much fat. Under pathological conditions, 
the quantity of fat in the blood may become so great that 
particles can be recognized microscopically between the red 
corpuscles, especially if they have been stained by osmic acid. 87 
This condition, known as lipsemia, is relatively uncommon. 
It occurs in various pathological conditions, especially in dia- 
betes, and is frequently merely transitory. 

In discussing the chemistry of the blood-serum, we shall 
consider especially the proportions of proteids, salts, and 
water. According to Hammarsten's analyses, 9.2 per cent. 
of the serum consists of solids, of which 7.6 per cent, are 
proteids. Since the proteids form the greater part of the 

M Rumpf, Virch. Arch., vol. clxxiv. p. 163. 

" Gumprccht, Dcut. mcd. Wochcnschr., 1894, No. 39. 



164 CLINICAL PATHOLOGY 

solid material in the serum, they and the water ordinarily 
vary in inverse ratio to each other, a high percentage of 
proteids being accompanied by a relatively low percentage of 
water, and vice versa. 

The proteids of the serum consist chemically of albumin 
and various forms of globulin. 88 Recent biological work, 
however, has shown such a variety in the proteids of the 
blood that we can no longer regard the above simple chemical 
division as in any way a final one; and when we remember 
that in all probability each organ contributes its quota to the 
blood, it seems impossible that the division into albumin and 
globulins could be any other than a mere classification of the 
proteids present under these group names. The serum of 
healthy men contains somewhat more albumin than globulin, 
the ratio being about 4.5 to 3.1. This ratio differs in different 
species of animals, and varies in the same individual under 
different circumstances. The earlier idea that the albumin 
diminishes during fasting has not been confirmed by later and 
more accurate work. 89 

The total quantity of proteids in the serum may be deter- 
mined either by precipitation methods or by determinations 
of the total amount of nitrogen present. The latter method 
is applicable only when we can be certain that there is no 
retention of nitrogenous by-products in the blood, the quan- 
tity of these substances, ordinarily present, being negligible. 
Since the total quantity of proteids in the serum varies roughly 
in an inverse ratio to the amount of water present, we will 
defer the consideration of their quantitative variations until 
we discuss the water in the serum. 

Our knowledge of the proteids of the blood has undergone 
a complete revolution within recent years. The researches on 
immunity have brought to light important functions of the 

88 Pick, Hofmeister's Beitr., vol. i. p. 351. 

89 See Haliburton's Text-Book of Physiological Chemistry. 



THE BLOOD 165 

blood which were hardly suspected previously. The substances 
which bring about these so-called biological reactions cannot 
be separated from the proteids by purely chemical means, 
though we have no direct proof that they are themselves of a 
proteid nature. 

Among the substances under consideration are those which 
possess the property of accelerating the decomposition of other 
compounds; 90 i.e., they are of the nature of ferments. If we 
may assume that the decomposition of different compounds 
requires the action of different ferments, then the number of 
ferments present in the blood must be considerable. For the 
physiologist, such a conception presents certain difficulties. 
The most varied reactions may be produced by the serum, and it 
would be necessary to assume a different ferment for each one 
of these reactions, many of which are apparently absolutely 
useless. For example, the blood-serum of the carp possesses 
the property of decomposing trehalose, and yet we have no 
reason to believe that trehalose is ever present in the blood 
of this fish. 

Substances present in the blood-serum may neutralize cer- 
tain poisons which may gain access to the blood, a property 
which is unquestionably of great value to the body. 

Cytolytic Properties of the Serum. — The blood-serum is 
able to destroy many varieties of foreign cells, among them 
living bacteria. According to our most recent knowledge, 
two substances participate in this destructive action. One 
of these possesses the properties of an enzyme, — viz., it is 
destroyed by a temperature of 56 C. for half an hour, and 
it acts best at a definite temperature and in a medium of a 
definite reaction and containing salts in certain proportions. 
In the blood of healthy individuals, this substance is always 
present, though in varying amounts. It has been called by 

*°E. Fischer and Nicbcl, Sitzungsbcr. dcr kgl. preuss. Akad. der 
Wissensch., 1896, p. 73. 



166 CLINICAL PATHOLOGY 

Buchner the alexin, and by Ehrlich and his school, the com- 
plement. Considerable controversy has arisen over the ques- 
tion as to whether there is one alexin in the blood, capable of 
destroying indifferently a great variety of cells, or whether 
there are a large number of different alexins present, each 
possessing a more or less specific destructive action upon cer- 
tain kinds of cells. The former view has been championed 
by Bordet and Buchner, the latter by Ehrlich and his school. 
The latter appears to me to be the more probable. It is sup- 
ported especially by those experiments in which the serum loses 
completely its power to destroy one variety of cells while 
retaining its power to destroy another variety. 

The alexins are believed to be produced by the leucocytes, 
some holding that they are secretions of these cells, others that 
they become free only when these cells die (Metschnikoff). 
Metschnikoff has advanced the hypothesis that different varie- 
ties of leucocytes produce different forms of alexins. 

In discussing the subject of haemolysis (p. 144), we have 
already stated that even the alexins of normal serum probably 
do not act alone. The other class of substances, which assist 
them, differ from the alexins in that they can usually resist 
temperatures of 6o° C. This second class of bodies is present 
in normal sera, but only in relatively small quantities. During 
the process of immunization against foreign cells, however, 
these bodies become enormously increased. They have been 
variously designated as the immune bodies (Pfeiffer), sub- 
stance sensibilisatrice (Bordet), fixateurs (Metschnikoff), and 
intermediary bodies or amboceptors (Ehrlich). These differ- 
ent names were given to indicate the conception of the namers 
as to the manner in which the bodies under consideration act. 

This second, intermediary body possesses a special affinity 
for those cells which are susceptible to its action. Owing to 
this fact, it is possible to remove the intermediary bodies from 
a serum. To do this, the cells and the serum are allowed to 



THE BLOOD 167 

stand for a certain time in contact at o° C, at which tempera- 
ture the intermediary body is bound by the cells, but the 
alexins are left free in the fluid. If the cells are now removed 
from the serum by centrifugalization, they carry with them 
the intermediary bodies, the alexins being- left behind. Differ- 
ent varieties of cells possess different affinities, and conse- 
quently will remove different intermediary bodies from the 
same serum. The subject is so intimately related to the theory 
of immunity that it will be again considered in that connection. 

The nature of the relation by which the intermediary bodies 
are bound to the susceptible cells has been the subject of much 
controversy, as is illustrated by the various names which have 
been applied to this body. Gruber and Metschnikoff believe 
that it favors in some way the action of the alexin on the 
cell. Bordet believes that it so changes the physical properties 
of the envelope of the red corpuscle that the alexin can " take 
hold" on it. Ehrlich regards it as a substance which combines 
chemically on the one side with the cell, and on the other with 
the alexin, and in this manner it permits the alexin to come in 
direct contact with the cell. According to Ehrlich's view, the 
alexin alone cannot act directly upon the cell, because it cannot 
combine with it chemically, and it is only through the interven- 
tion of the intermediary body that a combination is possible. 

Antitoxins : The " Side-Chain" Theory. — The blood- 
serum is able to neutralize the action of a variety of poisonous 
compounds. It is not our purpose to discuss the many methods 
by which the body protects itself against toxic substances. 
Some are rapidly excreted, some are rendered inert by chemical 
combinations in the organs, acids are neutralized by an in- 
creased production of ammonia, saponin is neutralized by 
soaps, 91 etc. 

If the toxins produced by the diphtheria bacillus be injected 
into an animal, the blood-serum of that animal will, after a 

01 Ransom, Dcut. med. Wochens., 1901, No. 13, etc. 



168 CLINICAL PATHOLOGY 

time, acquire the property of neutralizing the poisonous action 
of these toxins. The new substance to which the serum owes 
this property is called the diphtheria antitoxin. Other sub- 
stances, among them the tetanus toxin and the various snake 
venoms, will likewise give rise to the production of antitoxins 
if they be injected into living animals. Although the anti- 
toxin annuls the poisonous action of the toxin, the latter is not 
destroyed, for it may be recovered from mixtures of the two 
by certain manipulations, 92 and it has been demonstrated that 
the neutralization takes place in accordance with the laws of 
chemical combination. 93 

All are not yet agreed as to the principles underlying the 
formation of antitoxin in the body. According to Buchner's 
conception, the introduced toxin is itself converted into anti- 
toxin by the cells of the body. Behring 94 early expressed the 
view that the very substances in the living body which are 
attacked by the toxins are curative if they become free in the 
blood. 

Ehrlich has elaborated the same hypothesis into his now 
famous " side-chain" theory. If toxic substances of a proteid 
nature be injected into the circulation, they rapidly disappear 
from the blood, apparently because they are taken up by the 
cells. Since, however, they can no longer be recognized in the 
tissues, a fact which has been demonstrated for certain toxins, 
it is believed that they have entered into chemical combina- 
tion with the protoplasm of the cells. Ehrlich assumes that 
they have combined with peripheral groups of atoms on the 
large proteid molecules in the cells, which groups he designates 
as the side-chains. If toxins encounter appropriate side- 
chains in the body, they are held by such in combination. 

92 Calmette, Inst. Pasteur, 1895, p. 225 ; Wassermann, Ztft. f. Hyg., 
vol. xxii. p. 263. 

03 Arrhenius, Berl. klin. Wochenschr., 1904, p. 216. 
94 Deut. med. Wochens., 1898, No. 5. 



THE BLOOD 169 

Ehrlich further assumes that the injury done to the molecule 
by this fixing of the poisonous toxin on its side-chains acts as 
a stimulus to the production of new side-chains, similar in 
character to the ones which were originally injured or de- 
stroyed by the toxin. The number of these new side-chains 
produced is greatly in excess of the number originally de- 
stroyed, and the additional ones are thrown off into the circu- 
lation, where they remain, ready to combine with any new 
toxin which may appear there. These free side-chains in the 
blood, which possess a peculiar affinity for the toxins, are what 
are known to us as antitoxins. The original injury to the 
cell may be so severe, however, that the latter is unable to 
respond to the stimulus, and consequently no antitoxins are 
produced. The side-chain theory has been given a very 
wide application, not only to toxins, but to all foreign sub- 
stances which may combine chemically with the cells of the 
body. It has been offered as an explanation of the forma- 
tion of the intermediate immune bodies, of precipitins, agglu- 
tinins, etc., and even of the physiological assimilation of 
proteid food. 

It seems to us that the most vulnerable point in Ehrlich's 
theory is that relating to the production of new chains by the 
injured molecule. This has been likened to the reaction of 
tissues to an irritant, which reaction may be so excessive that 
the new tissue is produced in excess. The two processes are, 
however, fundamentally different; for, on the one hand, we 
are dealing with the reaction of living tissue, as a whole, to 
an injury, while, on the other, it is a reaction involving in- 
dividual molecules. No reaction, analogous to this one, is 
known to chemistry. 

The organs which clinically seem to suffer most from the 
infection are usually the ones with which the largest quanti- 
ties of toxin combine; and it has been demonstrated, for ex- 
ample, that the central nervous system possesses a peculiar 



170 CLINICAL PATHOLOGY 

affinity for the tetanus toxin. 95 Yet this is not necessarily the 
case, and even though the toxins combine with cells in the 
body, no symptoms may be produced, either because the cells 
affected are of relatively little functional importance, or be- 
cause the combination does not seem to greatly harm them. 
Certain animals, as the hen and the alligator, are practically 
insusceptible to tetanus, and yet when treated with the toxin, 
they yield antitoxin in abundance. In such cases it is probable 
that tissues, other than the nervous system, combine with the 
toxin without serious damage to themselves and with the 
production of antitoxin. Immunity to toxins may, however, 
occur in another way. Thus the tetanus antitoxin will remain 
in the blood of the turtle for a long time without giving rise 
either to the symptoms of tetanus or to the production of anti- 
bodies. In such a case, we may assume that the turtle pos- 
sesses no molecules in its cells with which the tetanus toxin 
can combine. 

When cells have been stimulated to the production of anti- 
toxin, they continue to produce it over a long period of time. 
For this reason the immunity acquired by passing through a 
disease is more or less durable ; for the same reason, the blood 
of animals strongly immunized may be repeatedly withdrawn, 
and yet that which is left will always develop new antitoxin, 96 
Similarly, the injection of pilocarpin will increase the amount 
of antitoxin in the blood, probably because it stimulates the 
internal secretion of the cells. 97 

Though antitoxin occurs in largest quantity in the blood 
of those who received the toxin, nevertheless it may be present 
in the blood-serum of a healthy individual, and even, indeed, 
in the serum of the new-born infant. This remarkable fact, 
which will be discussed in another place, is explainable in 

85 Wassermann and Takaki, Berl. klin. Wochens., 1898, No. 1. 

08 Roux and Vaillard, Inst. Pasteur, 1893. 

87 Salomonson and Madsen, Inst. Pasteur, 1897. 



THE BLOOD 171 

accordance with Ehrlich's hypothesis, on the assumption that 
for some reason the side-chains for which the toxin has an 
affinity have been cast loose into the circulation. 

As a rule, antitoxins act solely or, at least, most energeti- 
cally upon the toxins that called them into being. Exceptions 
to this rule, however, do occur, and Calmette has shown that 
the antitoxin for cobra venom will neutralize the venom of a 
variety of snakes and scorpions, and that tetanus antitoxin 
will likewise neutralize snake venom. (Yet even snake venom 
shows specific differences, for cobra antivenin will not neu- 
tralize the venom of the rattlesnake. 98 — Ed.) 

The Precipitins. — If proteid substances are injected into 
an animal, the blood-serum of that animal acquires the prop- 
erty of causing a precipitate when mixed with a clear solution 
of the proteid injected. The new substance in the serum 
which gives rise to this precipitate is called a precipitin." 
These precipitins cannot be separated from the globulins of 
the blood by chemical methods. 

The question has arisen as to whether these precipitins are 
specific tests for the proteids injected; i.e., will the blood- 
serum of an animal which has been treated with a certain pro- 
teid give a precipitate only with solutions of that proteid? 
This is not apparently the case. The specificity of the reaction 
seems to depend not upon the structure of the entire molecule 
injected, but upon the fact that it possesses certain atomic 
groups, and any proteid which happens to contain these groups 
might be precipitated by the precipitin. This question is one 
of considerable practical importance, for the precipitin reac- 
tion has been used to distinguish the bloods of different ani- 
mals. If the blood-serum of an animal, A, be injected into an 

M Flexner and Naguchi, Jour, of Med. Research, vol. xi., No. 2. 

80 R. Kraus, Wien. klin. Wochens., 1897, p. 736; Wassermann and 
Schiiltzc, Bcrl. klin. Wochens., 1901, p. 187 ; Uhlcnhuth, Deut. med. 
Wochens., 1901, p. 82; Ewing and Straus, Med. News, November, 1903; 
McIIall and Dinkclspiel, Jour, of Hyg., vol. i. p. 367. 



172 CLINICAL PATHOLOGY 

animal, B, then the serum of B acquires the property of caus- 
ing a precipitate if mixed with the serum of any animal of 
the A species, although no precipitate is caused if mixed with 
the serum of most other species of animals. If a blood-stain 
is suspected to be derived from the A species, it is only neces- 
sary to dissolve some of it in water and to test it with the 
serum of an animal which is known to have been immunized 
against the species A. If a precipitate results, after certain 
precautions are taken, it is very probable that the stain really 
was from an animal belonging to the species A. In carrying 
out such an examination, it is necessary to make use of quan- 
titative methods, similar to those used in agglutination tests. 
In this way it is possible to eliminate the possibility that the 
stain is derived not from the species A, but from some closely 
related species A'. Though the latter might cause a precipitate 
with the A precipitin, they will do so only in relatively strong 
concentrations. 

The precipitin reaction is favored by a slightly acid reac- 
tion, especially when that is produced by the organic acids, 
and the presence of salts of some kind is absolutely necessary. 
The precipitins are relatively resistant to unfavorable influ- 
ences. Temperatures of 6o° C. are borne for a considerable 
time, and drying or even putrefaction does not destroy them. 

Agglutination. — If foreign cells or bacteria be injected 
into an animal, the blood-serum of the latter acquires the 
property of causing these cells to collect in clumps, which fall 
to the bottom of the vessel leaving a clear fluid above them. 
This reaction is called agglutination. 100 

The relation of the process of agglutination to the de- 
struction of foreign cells is not yet perfectly clear. Some hold 
that the agglutinins are closely related to the intermediary 
bodies which assist in the destruction of foreign cells, and 

100 Gruber and Durham, Munch, med. Wochens., 1896, p. 285 ; Gruber, 
Munch, med. Wochens., 1899, No. 41. 



THE BLOOD 173 

which are also produced during the process of immunization; 
yet many facts indicate that the two are quite distinct. Agglu- 
tination seems to be caused by changes in the enveloping mem- 
branes of the cells which are agglutinated. 101 

The blood-serum therefore contains a great variety of 
substances, and is possessed of the most varied functions. Our 
knowledge of these matters is only in its infancy, and no one 
dares to surmise what the future may bring forth. According 
to the Ehrlich hypothesis, the agglutinins, precipitins, anti- 
toxins, intermediary bodies, etc., are derived from the cells of 
the body. We know little concerning the source of the normal 
proteids of the blood, such as the albumin, the globulins, and 
the fibrinogen; yet the differences in the bloods of different 
animals, as demonstrated by the precipitin reactions, would 
lead one to believe that these proteids are, in part at least, 
the products of cellular activity, and, as such, are quite inde- 
pendent of the character of the nourishment taken. It seems 
probable, indeed, that the proteid food not immediately con- 
sumed in the metabolism of the body is taken up by the cells 
and is transformed by them into the proteids of the plasma. 

The question as to the chemical nature of the various anti- 
bodies, particularly of the diphtheria and tetanus antitoxins, 
has been studied by Pick. 102 He has shown that they are pre- 
cipitated along with the globulins of the serum. The chemical 
characteristics of diphtheria antitoxin vary according to its 
source ; that from the goat being precipitated with euglobulin 
and that from the horse with pseudoglobulin. Such differ- 
ences were not discovered for the tetanus antitoxin, but were 
found true for certain agglutinins. These facts support the 
view that the " biological" properties of a substance depend 
not so much upon its total molecular composition as upon the 
possession of certain groups of atoms. 

101 See Sick, Arch. f. klin. Med., vol. Ixxx. p. 389. 

102 Hofmeister's Bcitr., vol. i. p. 351. 



174 CLINICAL PATHOLOGY 

The Salts of the Serum. — The salts of the serum are, for 
the most part, made up of sodium chloride, sodium carbonate, 
and the phosphates of the alkalies. Other salts are present 
only in minimal quantities, and some, such as calcium phos- 
phate, are present in the plasma, but are removed from the 
serum by the fibrin during coagulation. The variations of 
the salts of the blood in health and in disease have never 
been satisfactorily worked out, which is unfortunate, for with- 
out doubt the salts exercise an important influence upon the 
blood-corpuscles and upon the proteids of the plasma. 

The Percentage of Water in the Blood. Hydraemia. — The 
relative amounts of proteids and water in the serum vary even 
in health, although the limits of these variations are not accu- 
rately known. The variations in disease have only been par- 
tially studied ; but we know that they frequently remain within 
the normal limits, even in the most severe diseases. The most 
evident thickening of the blood — i.e., the greatest relative 
increase in the proteids — is seen in Asiatic cholera, and de- 
pends upon the loss of fluids from the body. 

When the unit of blood is deficient in proteid material, we 
speak of an hydraemia, a watering of the plasma. 103 This 
condition frequently develops as a result of emaciating dis- 
eases. If the heart and kidneys are in order, the hydraemia is 
probably due to a primary diminution in the proteids of the 
blood, although we must remember that a destruction of the 
proteids of the body does not necessarily produce a watery 
condition of the plasma. Among the emaciating diseases 
which may produce an hydraemia of this character are inani- 
tion, repeated hemorrhages, anaemias, malignant tumors, and 
severe chronic infections. Although an hydraemia frequently 
develops in the above diseases, nevertheless it does not neces- 
sarily do so. We are not justified, therefore, in concluding 

103 v. Limbeck, Prag. med. Wochens., 1893, No. 12; Hammerschlag, 
Ztft. f. klin. Med., vol. xxi. p. 475. 



THE BLOOD 175 

that a rapid consumption or a diminished supply of proteid 
material is alone responsible for the hydremias of this class. 
Other factors, at present little understood, undoubtedly play 
a part. Until we know more of the functions and source of 
the proteids of the plasma, it will be impossible to harmonize 
the many contradictory facts relating to this class of hydre- 
mias. 

It is possible that an hydremia should be caused, not by 
a primary reduction of the proteid constituents of the blood, 
but by a primary increase in the amount of water. The 
hydremias associated with the diseases of the kidneys and 
with cardiac insufficiencies are probably partly of this nature. 
According to Hammerschlag, chronic interstitial nephritis 
rarely causes a watery condition of the blood, and chronic 
parenchymatous nephritis sometimes fails to do so. Hydremia 
is frequently present in the latter, however, and it is most 
marked when there is polyuria. Under such circumstances, 
the specific gravity of the blood may fall from the normal of 
1.030 to 1.020. Other observers have obtained results which 
differ somewhat from those of Hammerschlag; yet some of 
these, based upon total nitrogen determinations, must be re- 
jected as inaccurate, on account of the frequent retention in 
nephritic blood of other nitrogenous bodies than proteids. 

The hydremia which is undoubtedly present in many cases 
of nephritis can be caused only in part by the loss of albumin, 
for the hydremia and the amount of albumin in the urine 
bear no definite relation to each other. In many cases of 
nephritis, water is retained in the body, for less is excreted 
through the kidneys and often less also through the skin. 
These two factors — the loss of albumin in the urine and the 
retention of water in the body — are sufficient to explain the 
hydremia present in many cases of nephritis, though hardly 
in all, for some patients with hydremia are excreting large 
amounts of urine. (The cause of the retention of water has 



176 CLINICAL PATHOLOGY 

recently been attributed to a primary insufficiency in the excre- 
tion of sodium chloride through the kidneys, the retained water 
serving merely to dilute the retained salt. In support of this 
hypothesis, we have Widal's observations that, in certain cases 
of nephritis, the oedema disappears with almost miraculous 
rapidity if the ingestion of chlorides be restricted. 104 — Ed.) 

Certain patients, suffering from heart disease in the stage 
of broken compensation, show a watery condition of the blood ; 
both the specific gravity and the proportion of proteids in 
the blood being diminished. 105 A weakness of the right ven- 
tricle is especially apt to give rise to such a thinning of the 
blood. When the circulation improves and the venous press- 
ure falls, then the blood tends to return to its normal com- 
position. This hydrsemia occurs in a comparatively small 
proportion of all cases of broken compensation; but, where 
it does occur, it is quite usual for it to disappear with any 
improvement in the circulation. In these cases, the loss of 
proteids from the blood is not usually very great, but there is 
frequently a retention of water which would tend to dilute the 
blood. 

It seems very probable to us that the hydremias which 
accompany cardiac and renal diseases are for the most part 
caused by such a retention of water in the body ; that there is, 
in fact, an increased quantity of watery blood in the body, a 
so-called hydrsemic plethora. Such an hypothesis would well 
explain the fact that with the development of a cardiac insuffi- 
ciency not only the proteids, but the number of corpuscles to 
the unit-volume of blood, is diminished, and that, with an 
improvement in the circulation, the blood again becomes nor- 
mal. There is no reason why the blood should not become 
oedematous just as do the tissues. Possibly, the water is held 

104 See, for example, the case described by Widal and Javal, Inter- 
national Clinics, fourteenth series, vol. i. p. I. 

105 Grawitz, Arch. f. klin. Med., vol. liv. p. 588. 



THE BLOOD 177 

back in the body by substances which attract it (see p. 175). 
Grawitz believes that the increased amount of water in the 
blood is derived from the lypmh which diffuses into the capil- 
laries, owing to the low pressure existing there. Yet we know 
that in the conditions under consideration fluids pass from 
the capillaries into the lymph-spaces, so that these become dis- 
tended. The relations must therefore be quite complicated and 
the final results dependent upon which process takes place the 
more rapidly. 

Polycythasmia. — In not a few cases of chronic stasis, the 
capillary blood is more concentrated than normal. At least 
it contains many more red blood-corpuscles and correspond- 
ingly more haemoglobin to the unit-volume. The compo- 
sition of the serum in these cases has not yet been finally 
settled, but good observers have found it to be diluted. 106 
This increase in the number of the erythrocytes is found 
especially in cases of long-continued venous stasis, such as 
occur in congenital heart lesions, in chronic pulmonary dis- 
ease, and in insufficiency of the right ventricle. Investiga- 
tions thus far have all been made upon the blood of the 
cutaneous capillaries or veins, so that we are unable to discuss 
the relative concentration of the blood in the different vessels 
of the body; 107 yet the possibility exists that in these cases of 
stasis, the blood of the peripheral vessels contains more cor- 
puscles than does the blood of the remainder of the body, 
and the question can only be decided by studies on fresh 
cadavers or upon animals with heart lesions. 

The number of erythocytes in these cases is often very 
great, — from six million to eight million per cubic millimetre; 
and, at the same time the serum is usually more dilute than 
normal. This latter fact would seem to indicate that the in- 
creased number of corpuscles is not due to a loss of water 

1<w Hammcrschlag, Grawitz, loc. cit. 

107 Grawitz, Arch. 1. klin. Med, vol. liv. p. 588. 

12 



178 CLINICAL PATHOLOGY 

from the blood. Marie and Hayem explain the increase in the 
number of red blood-corpuscles as a compensatory process 
which tends to neutralize the insufficient oxidation of the 
blood caused by the stasis ; 108 yet since their theory presup- 
poses an increase in the number of corpuscles throughout the 
whole body, it rests upon an insecure foundation. 

It is possible that the polycythemia is primary in certain 
cases; i.e., that it occurs without demonstrable cause. At 
least, there have been some remarkable cases reported in which 
chronic cyanosis, enlargement of the spleen, albuminuria, and 
increase in the number of the red corpuscles have been observed 
without any considerable venous stasis. 109 

Extremely interesting are the changes which take place in 
the blood when an animal passes from a region of high to one 
of low atmospheric pressure. Within a short period of time 
the number of red corpuscles to the cubic millimetre of blood 
becomes increased, and the haemoglobin also increases, but 
more slowly. These increases affect the blood of all parts 
of the circulatory apparatus, though they are less marked, 
perhaps, in the arteries than in the veins and capillaries of the 
skin. The higher the elevation, the greater is the number of 
red corpuscles. The highest figures which have been reported 
are from the Cordilleras, at an elevation of over twelve thou- 
sand feet. 110 All the animab at these heights have an ex- 
traordinary number of red corpuscles; e.g., the llama has 
sixteen million to the cubic millimetre. The amount of gas 
in the blood is, however, about the same as in the blood of 
animals at lower levels. When a man or animal descends from 
these heights to the sea level, the number of red cells dimin- 
ishes correspondingly. There is almost universal agreement 

ios p Marie, Merer, med., 1895, No. 3 ; Hayem, ibid., No. 4. 

109 Osier, Am. Jour, of the Med. Sci., August, 1903. 

110 Viault, Compt. rend, de l'acad. des sci., vol. cxi. p. 917; vol. cxii. 
P- 295. 



THE BLOOD 179 

among authors in regard to the increase in the number of 
erythrocytes per unit-volume at high elevations, and the few 
negative observations ni are due probably to too short a stay 
at the high altitude. At any rate, there is usually an increase 
in the number of the red cells per unit-volume at high altitudes. 

This increase is unquestionably caused by the low atmos- 
pheric pressure, for it can be produced experimentally by sub- 
jecting animals to low pressures under the air-pump. 112 Some 
consider that the total number of red cells in the body is 
actually increased in such cases, and that this serves to com- 
pensate for the lessened pressure of the oxygen in the lungs. 
If, indeed, new cells are formed, we have little microscopical 
evidence of it, for nucleated red corpuscles have been seen by 
very few, 113 and most authors expressly state that they were 
absent. Furthermore, it is difficult, on such an hypothesis, 
to account for the rapid disappearance of red cells when the 
animal returns to a lower altitude, for positive signs of a 
destruction of red corpuscles, such as jaundice and a deposi- 
tion of iron in the liver, have not been observed under these 
conditions. Yet we know that the absence of these signs is by 
no means absolute proof that no destruction of the red cells 
has taken place, for they have been missed in cases in which 
an extensive destruction certainly had occurred. 114 

Another explanation that has been offered for the increase 
in the number of the erythrocytes at high altitudes, is that it is 
due to a loss of water from the blood; yet this meets with 
almost equal difficulties. Beyond question, the dryness of the 
air, the exposure to the sun's rays, and the deeper respira- 
tions increase the loss of water from the body, yet a healthy 

111 Schumburg and Zuntz, Pfliiger's Arch., vol. lxiii. p. 492; Egli- 
Sinclair, Wien. med. Blat., 1895, Nos. 8 and 9. 

112 Gra\vitz, Berl. klin. Wochenschr., 1895, Nos. 33 and 34; Schauman 
and Rosenquist, Ztft. f. klin. Med., vol. xxxv. pp. 126, 315. 

ia Gaule, Pfliiger's Arch., vol. lxxxix. p. 119. 

"' Lesser, Verh. dcr Siich. Gescll. d. Wissenschf., 1874, p. 153. 



180 CLINICAL PATHOLOGY 

man would ordinarily replace this water by taking more fluids 
by the mouth. The supposed loss of water should also lead 
to a more concentrated serum, as well as to an increased 
number of red blood-corpuscles, and it is very doubtful if this 
concentration of the serum actually occurs. The sera of two 
rabbits in Basel contained 7.62 and 7.96 per cent, of solids 
respectively, whereas in Arosa, at a high elevation, the per- 
centages were 7.79 and 8.02, an inconsiderable change com- 
pared with the changes in the erythrocytes. 115 Grawitz 
found some increased concentration in the sera of animals 
which had been kept under low pressures in Berlin, but 
here again the increased concentration was in no way pro- 
portional to the increase in the number of the red blood-cor- 
puscles. Furthermore, a concentration of the blood by evapo- 
ration is only possible when the tissues likewise lose large 
quantities of water, 116 and such a loss of weight certainly does 
not occur either in men or in animals subjected to low atmos- 
pheric pressures. Finally, an increase in the number of ery- 
throcytes also takes place when the animals are prevented from 
losing excessive amounts of water by being kept in rarified air 
saturated with water vapor. 

According to a third theory, the increase in the number of 
red blood-corpuscles at high elevations is due to the passage 
of plasma out of the blood-vessels into the lymphatic system. 
At present this seems to be the most plausible explanation for 
the known facts ; yet it is also open to objections, especially 
to the fact that the red blood-corpuscles and the haemoglobin 
do not increase at precisely the same rate. 

The crucial test for deciding whether or not the haemo- 
globin actually increases at high altitudes would be the de- 
termination of the total quantity of haemoglobin in the body. 
If this be increased in animals exposed to low atmospheric 

115 Egger, Kongr. f. in. Med., 1893, p. 262. 

110 Czerny, Arch. f. exp. Path., vol. xxxiv. p. 268. 



THE BLOOD 181 

pressure, then we may assume that there is, indeed, a total 
increase in the red blood-cells and in their pigment under these 
influences. Unfortunately, the experiments which have been 
undertaken to decide this point have given contradictory re- 
sults. Some observers found no increase in the total amount 
of haemoglobin in the body, 117 others have found a slight in- 
crease, 118 while still others have found a marked increase. 119 
The inaccuracies in the methods for determining the total 
haemoglobin in the body probably account for these discrepan- 
cies in results. 

An increase in the number of the red blood-corpuscles to 
the unit-volume is also seen in phosphorus and carbon monox- 
ide poisoning, but we are ignorant as to its exact cause. 

Plethora. — There is no reason a priori why an increase in 
the total quantity of blood in the body should not take place, 
for it is known that the parenchyma of other organs may 
increase in bulk. It is, however, impossible to obtain direct 
proof of such an increase so far as human blood is concerned, 
for as yet we have no accurate method of determining the total 
quantity of the blood in man. 

The doctrine of an increased quantity of blood, a true 
plethora, played a great role in the older hematology, and 
various symptoms were believed to be caused by the " full- 
blooded" condition of the patient. While we must acknowl- 
edge that many of these cases will not stand the rigid criticism 
of modern times and that the anaemia of many of these indi- 
viduals was the probable cause of their symptoms, yet there 
arc certain facts which favor a belief in the occurrence of a true 
plethora. Thus many patients feel better after having been 
bled, and although this fact is in no sense a proof that a con- 
dition of plethora existed previous to the bleeding, yet it 

"• Bunge and Weiss, Ztft. f. phys, Chem., vol. xxii. p. 526. 
"■ Abderhalden, I 'is-. Basel, 1902. 
""Jaquct, Arch. f. cxp. Path., vol. xlv. p. 1. 



182 CLINICAL PATHOLOGY 

cannot be entirely disregarded. More important is the testi- 
mony of such pathologists as v. Recklinghausen and Bol- 
linger who give it as their impression that at autopsy many 
bodies seem abnormally rich in blood. That the amount of 
blood in animals may vary greatly not only in different species, 
but in different individuals of the same species, has been 
definitely proved by the work of Bergmann and Bollinger. 120 
They have demonstrated that the character of the food may 
exert a marked influence upon the total quantity of blood in 
the bodies of animals. 

We are justified in suspecting a condition of plethora 
whenever an individual, who habitually consumes excessive 
amounts of food and drink, and who has large muscles and 
much fat, shows a continual hypersemia of the surface of his 
body, and has an enlarged heart, a full pulse, and wide arteries. 
Although we may be unable to prove that a plethora exists in 
such individuals, nevertheless the experience of pathologists 
and the experimental evidence above referred to, both justify 
such a probable diagnosis. 

Certain observations seem opposed to the doctrine of 
plethora, more especially the fact that if animals are infused 
with sera or salt solution, the excess of fluid is rapidly removed 
from the circulation, and no increase in the total quantity of 
blood is produced. Yet the conditions of such an " acute" 
experiment are quite different from the chronic changes which 
are believed to lead to plethora in man, and furthermore, it is 
quite possible that under pathological conditions there may be 
an inability to thus remove large quantities of fluid from the 
circulation. 

We hold, therefore, that although the doctrine of a true 
plethora has not been absolutely proved, its existence is very 
probable. The long-continued ingestion of excessive amounts 
of food seems to be the most potent causative factor. Yet it is 

120 Bollinger, Munch, med. Wochens., 1886, Nos. 5 and 6. 



THE BLOOD 183 

apparently only one factor, and others of which we are now 
ignorant may play a part in its causation. 

The doctrine of a diminution in the total quantity of blood 
is as little capable of direct proof as is the doctrine of plethora. 
Yet the impression prevails among clinicians, as well as among 
pathologists, that it does exist, and that in the severe anaemias, 
especially, there is a diminution not only in the number of cells 
to the unit of volume, but in the quantity of blood as a whole. 



CHAPTER IV. 

INFECTION AND IMMUNITY. 

In this chapter we propose to consider the various means 
by which the animal body resists the invasion of pathogenic 
micro-organisms. 1 

The Portals of Entry. — The surfaces of the body are 
covered with innumerable bacteria. They live upon the skin 
and upon the mucous membranes of the mouth, the nose, the 
trachea, the vagina, and the gastro-intestinal canal. The ma- 
jority of these bacteria are quite harmless; yet virulent ones, 
such as the diphtheria bacilli, pneumococci, and streptococci, 
are not infrequently present, without necessarily doing any 
harm. 

These surfaces must, therefore, act as barriers to the 
entrance of bacteria; mainly because the intact epithelium 
opposes great resistance to the passage of any solid particles 
through it. For example, the mercury in blue ointment is ap- 
parently converted into a fatty-acid salt before it is absorbed, 2 
and fats are absorbed by the intestines only after they have 
been brought into solution. On the other hand, we know that 
leucocytes may wander in and out between the epithelial cells, 
and it seems probable that they may carry bacteria back within 
them. If, after being thus carried into the body, the bacteria 
survive the ingestion by the leucocytes, they might cause dis- 
ease; though how frequently an infection takes place in this 
manner is entirely unknown. 

^schoff, Ehrlich's Seitenkettentheorie, etc.; v. Behring, Deut. med. 
Wochens, 1898, No. 5; Ehrlich, Gesm. Abhandl. ii. Immun., Berlin, 1904; 
Metschnikoff, Immunity. 

2 Schmiedeberg, Grundr. d. Arzneimittellehre, 4th. ed. 
184 



INFECTION AND IMMUNITY 185 

In many acute infections there is present an obvious in- 
jury of the epithelium, which permits the entrance of bacteria 
into the body, as is well illustrated in the case of the skin. 
Tetanus, malaria, and the various wound infections nearly 
always gain admittance to the body through an injury of the 
cutaneous epithelium. 

Our knowledge of the method by which infections enter 
through the mucous membranes is less accurate. Tonsillar dis- 
eases appear to play an important role in predisposing to infec- 
tions with the pyogenic cocci. The wandering of the leucocytes 
through the epithelium of the tonsils and the frequent local 
lesions render them especially permeable to bacteria, and liable 
to be the gate-way which admits a general invasion of micro- 
organisms. 

The air-passages of healthy individuals, below the upper 
part of the trachea, are, as a rule, sterile. 3 Yet should the 
bacteria penetrate to the lungs themselves, the delicate epithe- 
lium of the alveoli would hardly prevent them from passing 
through. At any rate, we know that solid particles, if inhaled 
in great numbers, are often deposited in the pulmonary tissues, 
as occurs in the dust diseases. Many observers believe that 
bacteria may also enter the lungs in a similar manner when- 
ever many are present in the inspired air. Such invaders may 
cause diseases of the lungs themselves, or they may be carried 
to the neighboring lymphatic glands, there to grow or to 
be destroyed. The lungs appear to possess considerable ability 
to destroy bacteria which may reach them, 4 and even though 
they become inflamed, this inflammation may protect the re- 
mainder of the body from a general invasion. Indeed, it 
seems to be rare for a general infection to gain admittance to 

* F. Miiller, Munch, med. Wochcns., 1897, No. 49; Klipstein, Ztft. f. 
klin. Med., vol. xxxiv. p. 191 ; opposed to these is Durck, Arch. f. klin. 
Med., vol. lviii. p. 368. 

«Snel, Ztft. f. Hyg., vol. xl. p. 103. 



186 CLINICAL PATHOLOGY 

the body by way of the lungs without producing a primary 
disease of these organs or of their lymphatic apparatus. 

The main protection of the lungs against the entrance of 
bacteria is the winding path through which the air must travel 
in the nose, the pharynx, and the larynx. Solid particles in the 
air are caught by the mucus which covers this passage, and, 
although this mucus possesses but little bactericidal power, yet 
it is at least a poor culture medium, and the bacteria, when 
caught, do not multiply. The current in the mucus, caused by 
the ciliated epithelium, is so directed that it tends to carry all 
particles out through the trachea. 

The factors which favor an infection of the air-passages 
have been accurately determined in animals, 5 but our knowl- 
edge, so far as man is concerned, is more limited. A large 
number of micro-organisms in the inspired air undoubtedly 
favors infection, especially if, at the same time, the individual 
breathes deeply. The virulence of the bacteria inhaled is 
likewise of importance, and, finally, an inflammation of the 
upper air-passages greatly favors the migration of bacteria 
down into the lungs. Cooling or wetting of the surface of the 
body is generally believed to favor the development of infec- 
tious processes in the bronchi and lungs, and this is possibly so 
because the epithelium is injured by such agents. If the air 
does not pass through the winding upper respiratory tract, in- 
fection of the lungs is much more liable to take place. For 
this reason, a tracheal canula is always a menace, and many 
animals with weak respiratory muscles are practically certain 
to die if they breathe through such a canula. For this reason, 
also, inflammations of the air-passages are relatively frequent 
in mouth-breathers. 

The gastro-intestinal tract is continually receiving micro- 
organisms which have been swallowed in the food. Some of 

8 Klipstein, Ztft. f. klin. Med., vol. xxxiv. p. 191 ; Gobell, Diss. Mar- 
burg, 1897. 



INFECTION AND IMMUNITY 187 

these are quickly destroyed by the action of the acid in the 
gastric juice; yet, since the stomach begins to empty itself 
shortly after the food enters, and since the first acid secreted is 
bound by the proteids of the food, and since, finally, the gastric 
juice does not reach the interior of many large food particles, 
there always exists the possibility that virulent organisms will 
pass through the stomach into the intestines. 

Once in the intestines, it becomes a question as to whether 
or not the bacteria will penetrate the intestinal walls. We 
may say, in general, that solid particles do not readily pass 
through these walls, and that, with but few exceptions, all 
experiments have tended to show the effectiveness of the 
epithelial barrier. Yet we possess indirect evidence that bac- 
teria may pass through the walls of the intestines. Typhoid 
fever is apparently contracted in this manner, and tuberculosis 
has been produced experimentally in animals by feeding them 
bacilli. Do these organisms, however, pass through an intact 
mucous membrane, or is a primary lesion of the epithelium 
necessary ? Baumgarten has shown experimentally that tuber- 
cle bacilli rapidly disappear from the intestinal contents, and 
that a few may afterwards be found in the lymphatic follicles 
and glands of the intestines. 6 They seem to be carried in 
during the absorption of food. The manner in which each 
different organism penetrates the intestinal wall must, how- 
ever, be studied separately; for when an organism grows in 
the intestinal contents, as do the cholera and probably also 
the typhoid bacilli, then it may readily produce a slight in- 
jury of the epithelium through which it penetrates to the 
blood. 

Yet even if we admit that bacteria can penetrate the un- 
injured intestinal wall, they certainly do not do this easily, 
and many circumstances influence the process. In the first 
place, the number of bacteria present is of great importance. 

* Ztft. f. klin. Med., vol. x. p. 49. 



188 CLINICAL PATHOLOGY 

Then, too, a rapid transit through the intestines may serve 
as a protection against invasion. Possibly this is the reason 
that many diseases of the intestines, such as typhoid fever, 
affect principally the ilium, where the passage of the contents 
is slower than it is in the jejunum, and where the organisms 
have a better chance to cling to the walls and to grow into 
them. 7 The normal flora of the intestines may be able to 
protect us from disease by killing off strange bacteria, and 
many pathogenic micro-organisms, if introduced into the in- 
testines, rapidly disappear without giving rise to any symptoms. 

The relations in the vagina are somewhat similar to those 
in the intestines. There, also, we have a normal flora, which 
may injure strange invaders, and the acid reaction of the 
secretions of the vagina is unfavorable to the development of 
most pathogenic bacteria. 8 

From all that has been said, we see what numerous de- 
fences against the invasion of micro-organisms are present on 
the surfaces of the body. The difficulty of passing the intact 
epithelium, the acidity and bactericidal properties of many of 
the secretions, the conflict with the normal flora and with the 
leucocytes on the surfaces, — all these serve to protect the body 
from the entrance of bacteria. In recent years there has been 
a tendency to lay too great stress upon the protective mechan- 
isms which are called into play after the organisms have 
entered the body. v. Behring has called attention to the fact 
that an animal may be highly susceptible to inoculation with a 
micro-organism, and yet be quite insusceptible to the cor- 
responding natural disease, apparently because it is able to 
prevent the entrance of the organism to its body (mouse 
anthrax ° ) . The defences of the body, therefore, begin at its 
surfaces, and these defences are of no little importance. 

7 Bienstock, Die med. Woche, igoi, Nos. 33, 34. 

8 Menge and Kronig, Bakt. d. weib. Genitalkanals, Leipzig, 1897. 

9 Diphtherie, in the Bibliothek Coler, Berlin, 1901, p. 95. 



INFECTION AND IMMUNITY 189 

Natural Inherited Immunity. — The ability of different per- 
sons to resist infection varies. Of the many exposed to a 
disease, only certain individuals contract it, although we may 
frequently be certain that many others have received the patho- 
genic bacteria into their bodies. Certain bacteria may be very 
pathogenic for one species of animals, and yet be almost with- 
out effect upon other closely related species. Even the re- 
sistance of the same individual varies under different circum- 
stances. 

Bacteria which have been introduced into the body may be 
rapidly destroyed without producing any symptoms of disease ; 
in which case the animal is said to be immune to the disease in 
question. This immunity may be an inherited one, or it may 
have been acquired by having had the disease in question, or, 
finally, it may have been produced artificially by means which 
will be discussed shortly. 

In the immune animal, organisms are rapidly destroyed 
without producing any harmful effects. How is this accom- 
plished? We know that bacteria are very susceptible to 
changes in the medium in which they live, and some have held 
that such changes cause the death of bacteria which have been 
introduced into the body. For example, unfavorable osmotic 
relations may kill bacteria, and changes in temperature may 
also be unfavorable to bacterial growth ; but it is doubtful 
if such changes exert any considerable influence in protecting 
warm-blooded animals, at least, from bacterial invasions. 

The plasma and serum of the blood are frequently able to 
destroy bacteria or to neutralize bacterial toxins. 10 Of this 
there can be no doubt. When bacteria are placed in a serum 
possessing bactericidal properties, they are broken up into small 
granules and ultimately dissolve, which solution may or may 

10 Nuttall, Ztft. f. Hyg., vol. iv. p. 253 ; Nisscn, Ztft. f. Hyg., vol. vi. 
p. 487; Bchring and Nissen, Ztft. f. Hyg., vol. viii. p. 412, and vol. ix. 
P- 95- 



190 CLINICAL PATHOLOGY 

not be preceded by an agglutination of the bacteria. This 
bactericidal property is lost if the serum be heated to 56 C. for 
half an hour. It seems very unlikely that such a temperature 
should change the nutritive or osmotic characters of the serum 
to any great extent, and for this reason it has been assumed 
that the bactericidal properties of the fresh serum are due to 
the possession of a ferment-like body, which is unable to resist 
a temperature of 56 C. These bactericidal substances are 
present, not only in the blood, but in the lymph and in extracts 
of various tissues. 

Yet the natural immunity of an animal and the bactericidal 
properties of its serum do not necessarily vary together. They 
do, indeed, do this in many instances, as, for example, in the 
case of the white rat, which possesses both a natural immunity 
against anthrax and a blood-serum which is capable of destroy- 
ing anthrax bacilli. On the other hand, there are many ex- 
ceptions to this rule. For example, the blood-serum of rabbits 
will destroy anthrax bacilli, whereas the animals themselves are 
susceptible to the disease. 

Natural Acquired Immunity. — An immunity against future 
attacks is frequently acquired by having passed through a 
disease; though not every disease leaves the patient thus im- 
mune against future attacks. Such an acquired immunity is 
most marked after the acute exanthemata. After typhoid 
fever it may last many years, or may, indeed, be permanent. 
Diphtheria and cholera reduce the susceptibility to future in- 
fections only for a very limited period of time. Pneumonia 
does not even do this, and erysipelas seems to leave behind, 
in many persons, an increased susceptibility to future infections. 
No relation exists between the severity of the infection and the 
degree of immunity acquired by having passed through it ; and 
it is a well-known fact that the mildest form of a disease may 
endow the individual with a substantial protection from future 
attacks. 



INFECTION AND IMMUNITY 191 

The cause of the immunity which results from the acute 
exanthemata has not been studied, mainly because we are 
ignorant as to the etiology of these diseases. The immunities 
resulting from typhoid fever and cholera have been carefully 
studied, and we know that they are associated with an increase 
in the bactericidal power of the blood. This increase in bac- 
tericidal power holds, not for all bacteria, but only for those 
which were the cause of the disease, or, in some instances, for 
closely related species also. Such a bactericidal immunity is 
identical with that acquired against other foreign cells which 
may have been injected into an animal, and the subject has 
already been discussed in speaking of the hemolytic power 
acquired by the injection of red blood-corpuscles (see p. 143). 

An acquired immunity does not, however, necessarily de- 
pend upon an increase in the bactericidal properties of the 
blood. In certain diseases it is due to the production of 
bodies which will neutralize the bacterial toxins; i.e., it is an 
antitoxic immunity. The majority of bacteria seem to harm 
the animal by the poisons which they produce, though the 
existence of such poisons has not been demonstrated for all, 
notably not for the anthrax bacillus. The classical examples 
of organisms which do produce such toxins is furnished by the 
diphtheria and tetanus bacilli. The danger of infections with 
these bacilli lies not so much in the extent of their growth as 
in the amount and virulence of the toxins absorbed, even when 
the infection itself is purely local. 

In some instances the toxins are to be regarded as the 
secretions of living bacteria, while in other cases they seem 
to be set free only when the bacteria die and their bodies pass 
into solution. The exact nature of this second class of toxins 
is very little understood. 

We know but little concerning the chemical nature of 
toxins. They are precipitated along with certain forms of 
proteids, but it is very questionable if they are proteids them- 



192 CLINICAL PATHOLOGY 

selves. Their extraordinary toxicity and the fact that they 
are extremely susceptible to heat incline one to believe that 
they are of the nature of ferments. 

The method of dissemination of the tetanus toxin is quite 
different from that of any known alkaloidal poison. While the 
latter are carried to the susceptible cells by the blood-current, 
the tetanus toxin travels through the nerves from the point of 
infection to the central ganglion cells, where it exerts its 
poisonous actions. 11 These ganglion cells cannot be reached 
by way of the blood-current, though they are affected by in- 
jections of the toxin directly into the nerves or into the spinal 
cord. When the injections are made into the cord, the in- 
cubation period, intervening before the development of symp- 
toms, which is otherwise so prolonged in tetanus, is much 
shortened or entirely absent. The incubation period for 
tetanus, therefore, appears to be the time consumed by the 
toxin in travelling from the point at which it enters the body 
to the cells upon which it exerts its poisonous action. This 
mode of dissemination explains the fact that in experimental 
tetanus the spasm first develops in the extremity infected; for 
the toxin, travelling up the nerve, first acts upon the corre- 
sponding part of the cord. In man, however, the muscles of 
the jaw are usually first affected. The diphtheria toxins, in so 
far as they affect the nervous system, may likewise travel 
along the nerves, for it is a well-known clinical fact that the 
nerves most frequently paralyzed are those which are situated 
in the neighborhood of the local lesion. 

Bacterial toxins, introduced into the body, lead to the 
formation of substances which possess the property of neu- 
tralizing the toxins introduced. These antitoxins have already 
been considered in another place (p. 167), and are of the 
utmost importance in the process of recovery from a disease. 

Besides the protection afforded to the body by the produc- 
" Meyer and Ransom, Arch. f. exp. Path., vol. xlix. p. 369. 



INFECTION AND IMMUNITY 193 

tion of antitoxins and bactericidal substances, the natural 
resistance may be increased by still other substances, which are 
not specific in their action. Years ago, Wooldridge showed 
that animals could be protected from anthrax by injections of 
his " tissue fibrinogen ;" and since then we have become 
acquainted with a great number of means which are more or 
less protective against a great variety of infections. 12 The 
immunity conferred by these means, however, is non-specific 
for a single bacterium, and is less certain, weaker, and less 
durable than is the immunity conferred by the specific anti- 
bodies; though, as we shall see, the passive, acquired im- 
munity is also of a fleeting character. 

The acquired, specific immunity may, therefore, be pro- 
duced by changes in the fluids of the body, in which case it is 
usually either a bactericidal or an antitoxic immunity. 

Active Artificial Immunity. — Immunity to an infection 
may also be induced by certain artificial means. There are two 
general methods of producing such an artificial immunity. 
In the first, the organism which causes the disease, or some 
material derived from it, is injected into the individual to be 
immunized. The latter then passes through a sickness with 
fever, etc., following which he becomes more or less immune 
to future infections with this same organism. An immunity 
acquired in this manner is termed an isopathic or active im- 
munity, because it is acquired by having had the disease. In 
practising this form of immunization, the material used is 
either injected in very small amounts or its virulence is weak- 
ened, so that the animal shall acquire the disease in a mild 
form. The immunity following such procedures develops 
gradually, but it is very durable, and even though antibodies 
are withdrawn from the body by bleeding, new ones are 
formed. As examples of active artificial immunization, we 
may name the antitoxic immunity of horses treated by injec- 

"Buchner, in Penzoldt-Stintzing, third cd., p. 119. 
13 



194 CLINICAL PATHOLOGY 

tions of the diphtheria toxins, the immunity against anthrax 
acquired by animals after injections with attenuated anthrax 
bacilli, the Pasteur treatment of rabies, and, finally, if we 
regard vaccinia as attenuated variola, the immunity to small- 
pox which follows vaccination. 

Passive Artificial Immunity — The second form of arti- 
ficial immunity is produced by the injection into the animal 
body of antibodies which have been produced in another ani- 
mal. For this purpose it is usual to use the blood-serum of 
animals which have acquired an active immunity to the disease 
in question. This passive immunity appears immediately after 
the injection, but it soon disappears, usually in the course of a 
few weeks, probably because antibodies produced in another 
animal are in the nature of foreign substances, and so are 
rapidly eliminated. The cells of the immunized animal seem 
to take no part in the process of passive immunization. 13 Pas- 
sive artificial immunity may be theoretically produced either 
by the injection of substances which will neutralize the 
bacterial toxins or by substances which will kill the bacteria. 
Practically, however, the latter (bactericidal sera) have not 
proved very successful, and the most notable examples of this 
method of immunization are the immunities produced by the 
injection of diphtheria and tetanus antitoxins. 

Phagocytosis and Immunity. — Up to this point we have 
discussed mainly the relation of the fluids of the body to the 
condition of immunity. There is, however, a school which 
places greater emphasis upon the part played by the living cells 
in the defence against disease. Wandering cells, partly leuco- 
cytes and partly derivatives of the fixed cells of the tissues, 
may pick up solid particles of all kinds and carry them away. 
Such cells are usually found in the neighborhood of solid 
particles, and they not only remove the latter mechanically, 
but may dissolve completely the substances ingested. This 

13 Fraenkel and Solbernheim, Hyg., Rundschau, 1894, pp. 97, 145. 



INFECTION AND IMMUNITY 195 

solution of foreign bodies appears to be accomplished through 
enzymes within the wandering cells. Sometimes the ingested 
body is not entirely dissolved, but is broken up into many 
smaller particles, which are removed with comparative ease on 
account of their small size. 

These wandering cells appear during the course of many 
infectious diseases. As has been stated in another place, they 
are attracted to the point of infection by substances derived 
from the bacteria in question. The process of picking up and 
removing foreign bodies in this manner is called phagocytosis, 
and the theory that immunity depends largely upon the phago- 
cytic properties of the cells has been developed especially 
through the work of Metschnikoff and his school, and has been 
defended by them with wonderful skill against numerous 
attacks. 14 

That wandering cells do pick up bacteria is established 
beyond question, and that they will pick up living bacteria is 
likewise certain, for Metschnikoff was able to cultivate anthrax 
bacilli which had previously been taken up by the leucocytes. 
In many infectious diseases, the greater number of bacteria 
present are found within wandering cells at the point of in- 
fection. Yet there are certain infections in which no such 
phagocytosis is to be seen, and in such the defences of the 
body must reside in its fluids; though Metschnikoff's con- 
tention that the protective properties of the fluids themselves 
are derived from wandering cells is not easily disproved. 

Conclusions. — No one theory of immunity, therefore, ap- 
plies to all cases, and it is very questionable if the body limits 
itself to one method of defence against the attacks of invading 
bacteria. Perhaps different methods are used in different cases, 
according to the manner in which the invading micro-organism 
attacks the individual. 

The body fluids of a person who is immune, either naturally 

14 Metschnikoff, Imnumitat bci Infcctionskrankh., Jena, 1902. 



196 CLINICAL PATHOLOGY 

or from having had the disease, may in certain instances 
possess the property of killing the invading micro-organisms 
or of neutralizing their toxins. In other instances, the wan- 
dering cells may pick up the bacteria and destroy them. Both 
processes may afford protection against the invasion of bac- 
teria, yet instances are known in which neither seems to ex- 
plain the immunity present, — e.g., the immunity of turtles 
against tetanus toxin (p. 170). 

In those infectious diseases in which the micro-organism 
does harm by means of the toxins which they produce (and 
this may be the case in all infectious diseases) death results 
if the amount or the virulence of the toxins cannot be neutral- 
ized by the infected animal. Cure follows the formation or 
the artificial introduction of a sufficiently large amount of 
antitoxin. We know that diphtheria bacilli are readily killed 
by the body if their offensive weapons, their toxins, can be 
rendered inert. But it also appears to be possible that the cure 
could result from a dying out of the bacteria even though 
their toxins have not been neutralized by antitoxins. Finally, 
the toxins, even though present, may cease to have power to 
affect the cells, for the reason, apparently, that the cells possess 
no molecules with which these toxins can combine, as has 
been shown especially for tetanus. 15 From a consideration of 
all these facts, it is evident that the protection which an animal 
enjoys from an infection may be due to any one or several 
of various factors, and that at present we are merely standing 
on the threshold of an accurate knowledge of the various 
means by which the body is protected against disease. 
15 Vincenti, Deut. med. Wochens., 1898. 



CHAPTER V. 

THE RESPIRATION. 

The cells of our bodies continually receive oxygen from 
the blood and continually give up the carbon dioxide formed in 
their metabolism to the blood- and lymph-streams. In the 
lungs the blood takes up a new supply of oxygen from the 
inspired air and unburdens itself of the carbon dioxide that 
it has received from the tissues. These processes, as a whole, 
are called respiration. The interchange of gases between the 
tissues and the blood is called internal respiration, whereas 
that between the blood and the air is called external respiration. 
Both are intimately dependent upon each other, and the inter- 
change of gases in the tissues, for example, is readily influ- 
enced by any changes in the lungs. 

The External Respiration — The first condition necessary 
for external respiration is the unhindered entrance of air into 
the lungs. In the pharynx the alimentary and respiratory 
tracts cross each other, and a special mechanism is therefore 
necessary to prevent the food from entering the air-passages, 
where it might produce a serious inflammation. This mechan- 
ism will be discussed in another place (p. 235). 

Means for removing Harmful Material from the Air- 
Passages, (a) Movements of the Cilia. — If foreign bodies 
do pass through the glottis into the trachea or its branches, they 
meet forces that tend to carry them out again. In the first 
place, there are the cilia on the epithelial surfaces, which, by 
their slight but continual motion, tend to carry all foreign 
particles from the bronchioles into the larynx. We are quite 
ignorant concerning pathological disturbances of the move- 
ments of these cilia; which is unfortunate, for it seems prob- 
able that a more definite knowledge would aid us in under- 

197 



198 CLINICAL PATHOLOGY 

standing the causation of many diseases of the lungs and 
bronchi. The movements of the cilia seem to be the most 
important factor in the removal of foreign particles from the 
smaller bronchi and the alveoli. Inflammatory material must 
also be removed from these regions, for otherwise serious harm 
to the lungs may result. 

(b) The Mucus. — The second mechanism that aids in pro- 
tecting the lungs is the secretion of mucus upon the surfaces 
of the air-passages. 1 Small bodies, such as particles of coal- 
dust and bacteria, are caught in this mucus, thereby being pre- 
vented from penetrating into the air-cells; and after being 
caught they are carried away by the action of the ciliated 
epithelium. Only when the secretion of mucus or the move- 
ments of the cilia are faulty, or when bacteria are inspired in 
great numbers, can the latter penetrate into the bronchioles 
and alveoli. 

(c) Sneezing. — The secretion of mucus and the move- 
ments of the ciliated epithelium are of the utmost importance 
in cleansing the lungs of foreign material. Certain other 
mechanisms, however, assist them. For example, many sub- 
stances are recognized from their odor as being harmful, and 
these are avoided by the patient. Sneezing tends to remove 
foreign bodies from the nose. After a deep inspiration, the 
air is forced out with great velocity, mainly through the nose. 
The combination of movements which constitute sneezing is 
initiated by reflexes proceeding from the nasal mucous mem- 
brane. Such reflexes are caused either by some excessive 
stimulation of the normal mucous membrane or by a slight 
stimulation acting upon a hypersensitive mucous surface. 

(d) Coughing. — Coughing is correspondingly of great 
importance in ridding the trachea and larynx of foreign 
material. It, also, is induced by a reflex mechanism; in 
the great majority of cases through the pneumogastric nerve. 

1 Miiller, Munch, med. Wochens., 1897, No. 49. 



THE RESPIRATION 199 

This nerve may be stimulated from the larynx, from the pos- 
terior part of the trachea, at the bifurcation of the trachea, 
from the diseased pleura, from a pathologically enlarged 
spleen or liver, 2 and, according to the views of many, from 
the stomach and uterus. 3 

The act of coughing is initiated by a deep inspiration. This 
is followed by a powerful contraction of the expiratory muscles. 
At first, the air that should be forced out meets the obstruction 
of a closed larynx; but later, the vocal cords separate, and 
through the opening the air is propelled with great violence. 
The soft palate closes the passage into the nose, and the cur- 
rent of air carries whatever is in the larynx or trachea up into 
the mouth. Possibly the contents of the larger and even those 
of the smaller bronchi may be removed by coughing, though 
this is much less likely to happen. In my opinion, the move- 
ments of the ciliated epithelium play the main part in trans- 
porting material from the alveoli up to the bifurcation of the 
trachea. When it has reached this point, the act of coughing 
readily carries it into the mouth. 

The nervous centre for coughing lies in the medulla near 
the respiratory centre. It is ordinarily excited by reflexes from 
the regions innervated by the tenth nerve, which regions have 
just been named. That it may also be directly put into action 
through cerebral influences is rendered probable by many facts, 
especially by this, that we are able to cough voluntarily. A 
reflex cough from the regions that have been named occurs 
when they have been stimulated beyond a certain point. The 
amount of stimulation necessary to provoke coughing may, 
however, vary. We may say, in general, that the irritability of 
the nerves is increased by acute inflammations of the mucous 

1 Naunyn, Arch. f. klin. Med., vol. xxiii. p. 423. 

"Edlefsen, Arch. f. klin. Med., vol. xx. p. 200; for a discussion of this 
subject see A. Fraenkcl, Diagnostik and Symptomatologie der Lungen- 
krankheiten, p. go. 



200 CLINICAL PATHOLOGY 

membranes, so that coughing is then produced by abnormally 
slight stimulation; while, on the other hand, certain drugs, 
as well as certain diseases of the brain, diminish the irritability 
of the nervous mechanism, and so diminish the tendency to 
cough. Chronic inflammations of the mucous membranes also 
have this effect in some instances. 

In the first class of cases, coughing may be induced by 
very slight chemical or physical changes in the inspired air; 
in the second class, no coughing results from stimuli that would 
otherwise be effective. An absence or weakness of coughing 
may likewise result from disease of the motor nerves or of 
the muscles concerned, as has been observed in serious lesions 
of the nervous system, as well as in patients with general 
muscular weakness. 

A diminution in the ability to cough in response to the 
normal stimuli is a source of danger, for secretions and foreign 
bodies are not properly removed from the lungs. This danger 
is much enhanced when the movements of the ciliated epi- 
thelium are also interfered with. Every physician knows and 
fears the results of such conditions, which are most frequently 
met in the aged, in those greatly weakened by disease, and 
during deep narcosis. 

Material retained in the lungs decomposes readily. We 
do not know certainly whether the micro-organisms that cause 
the decomposition are already present in the lungs, or whether 
they are introduced from without owing to the lack of protec- 
tive influences. Personally, I consider the latter the more 
probable, for many observers have found the normal lungs 
sterile, 4 though others have found pathogenic organisms in the 
lungs of healthy animals. 5 At any rate, the act of coughing 
is normally of great importance in protecting the lungs against 

4 See Barthel, Ztrbl. f. Bakteriol., vol. xxiv. Pt. I. pp. 401, 576. 
6 Diirck, Arch. f. klin. Med., vol. lviii. p. 368 ; Ztrbl. f. Bak., vol. xlii. 
Pt. I. p. 574- 



THE RESPIRATION 201 

disease, for it assists in removing both foreign material and 
excessive secretions. 

On the other hand, coughing is a useless act when it is 
caused by an abnormal irritability of the air-passages or by 
reflexes from other organs ; whenever, in fact, it occurs without 
there being something to be removed. It is then not only 
useless, but disadvantageous, for coughing greatly increases 
the intrathoracic pressure, and so interferes with the entrance 
of the venous blood into the chest cavity. It likewise raises 
the general arterial pressure. During coughing, therefore, 
there is danger of rupturing an artery, and the venous flow 
to the heart is lessened. Coughing also distends the lungs, 
owing to the increased pulmonary pressure, and a chronic 
cough may thus lead to a loss of pulmonary elasticity. For all 
these reasons, coughing per se is harmful, and, unless it serves 
to remove material from the air-passages, it should be con- 
trolled so far as possible. 

Stenosis of the Air-Passages. — A deficient interchange of 
gases in the lungs may arise from a stenosis of the air-passages. 
The results of such narrowings differ materially according to 
their locations. If the passage through the nose be completely 
occluded, it may be troublesome at first, but the adult soon 
learns to breathe through the mouth and to take his food as 
usual. Not so with the nursing infant. It cannot nurse 
properly if the nasal passage be closed, and the condition may 
then be very serious, on account of the interference with the 
ingestion of food. 

A stenosis of the larynx or trachea is much more serious. 
This may arise, first, from processes which compress the 
trachea, such as goitres, mediastinal tumors, and aneurisms; 
and, secondly, from diseases within the air-passages, especially 
from swellings of the mucous membrane of the larynx. The 
more narrow the passage, the more easily is it closed by such a 
swelling, and for this reason a swelling of the glottis in 



202 CLINICAL PATHOLOGY 

children is especially dangerous. The manner in which the 
majority of the forms of stenosis of the larynx produce the 
obstruction is easily understood, and need not be discussed. 
Less understood are those forms which begin very suddenly, 
last for a few minutes or hours, and then as suddenly dis- 
appear. To this class belong pseudocroup, spasm of the glottis, 
and whooping-cough. We believe that there can be no doubt 
that, in all these conditions, the essential factor is a spasm 
of the muscles which approximate the vocal cords. In addition, 
there is, in pseudocroup, an extremely acute inflammation of 
the mucous membrane, which can be seen under favorable con- 
ditions and which persists for hours after the cessation of the 
paroxysm, being accompanied by the symptoms of cough and 
hoarseness. In whooping-cough there is, in the great majority 
of cases, no inflammation of the laryngeal mucous membrane, 
and the paroxysms are here produced solely by a spasm of the 
muscles which close the glottis. We do not know exactly what 
causes this spasm in whooping-cough. So-called spasm of the 
glottis usually affects rhachitic children, and it is not infre- 
quently associated with enlargement of the thymus gland and 
with the symptoms of tetany. Here again the cause of the 
spasm is unknown. 

If there is an obstruction to the entrance of air into the 
lungs, the relative amount and the partial pressure of the car- 
bon dioxide in the alveoli increase, whereas the relative amount 
and the pressure of the oxygen decrease; so that the inter- 
change of gases with the blood proceeds at a slower rate than 
normally, and, unless some compensatory mechanism comes 
into play, the blood leaves the lungs abnormally poor in oxy- 
gen and abnormally rich in carbonic oxide. 

Stenosis of the trachea or of the larynx leads to changes 
in the respiratory movements which tend to produce a better 
aeration of the blood. We know that variations in the gases 
of the blood act directly upon the respiratory centre, and that 



THE RESPIRATION 203 

the latter is stimulated both by a lack of oxygen and by an 
excess of carbon dioxide. It would, however, be beneficial if 
the respiratory movements were increased even before any 
actual change in the character of the blood took place; for 
by this means it might be possible to compensate completely 
for the hinderance to the entrance of air into the lungs before 
the body could be harmed. There is reason to believe that 
this does, indeed, occur. The vagus fibres, which may 
strengthen both inspiration and expiration, are stimulated by 
a diminished intra-alveolar pressure. In stenosis of the larger 
air-passages, a transitory, abnormal, negative pressure is pres- 
ent in the alveoli at the beginning of inspiration, because the air 
does not enter the chest cavity freely. This negative pressure 
probably leads to an increase in the inspiratory movements 
through a stimulation of the vagus nerves. In more advanced 
stenosis, the gases of the blood are unquestionably altered, 
and the increase in the carbon dioxide is especially potent in 
stimulating the respiratory centre and in causing deeper 
respirations. 

If the inspirations become deeper from any cause, the 
ordinarily inspiratory muscles contract more forcibly, and new 
groups of muscles become innervated from the respiratory 
centre. Whenever the air cannot enter the chest cavity readily, 
a considerable negative pressure prevails there during in- 
spiration, and the softer parts of the thorax are pressed in by 
the atmospheric pressure without. There results the well- 
known inspiratory retraction of the epigastrium, of the lateral 
portions of the chest wall, and of the soft tissues above the 
sternum and clavicles. This is especially striking in cases of 
laryngeal stenosis. 

The respirations accompanying laryngeal or tracheal sten- 
osis are not only more powerful than normal, but are also 
of longer duration. We know that when the distention of 
the lungs has reached a certain limit, expiration is initiated by 



204 CLINICAL PATHOLOGY 

a reflex through the vagus nerve. In tracheal stenosis, the air 
cannot enter the lungs freely. They do not therefore become 
distended so quickly as in health, the reflex through the vagus 
is delayed, and inspiration is prolonged. Expiration is like- 
wise lengthened because the air cannot easily escape from the 
lungs on account of the stenosis. 

Normally, expiration is a purely passive act, due to the 
elastic contraction of both the chest wall and the lungs ; but in 
the conditions under consideration, expiration becomes active, 
being assisted by the contraction of certain muscles, which 
tend, on the one hand, to force the diaphragm up, and, on the 
other, to compress the thorax laterally. In stenosis of the 
trachea and larynx, therefore, expiration is lengthened, is 
more powerful, and is converted from a passive into an active 
process. 

This slow respiration of stenosis is directly beneficial to the 
patient. Experimental work has shown that, if the trachea be 
artificially narrowed, a slow rate of breathing allows more 
air to enter and to escape from the lungs than does the ordinary 
rate under the same conditions. 6 It is true that the extra 
exertion involved consumes more oxygen, but this is more 
than neutralized by the greater supply of that gas. 

In paralysis of the posterior crico-arytenoid muscles, in- 
spiration alone is interfered with, for it is their function to 
retract the vocal cords during inspiration. Should they fail 
to do this, the cords are sucked downward and together as 
the air enters, and this produces an inspiratory stenosis, even 
though the passage is perfectly free during expiration. Mem- 
branes and polyps which float loosely above the glottis may 
likewise give rise to an inspiratory dyspnoea, while those 
below the larynx may produce an opposite effect. 

The entrance of air into the alveoli may also be hindered 
by narrowings of the coarser or finer bronchi. In such cases 
8 Kohler, Arch. f. exp. Path., vol. vii. p. i. 



THE RESPIRATION 205 

the results depend entirely upon the site and extent of these 
narro wings. If the main bronchus on one side be obstructed, 
then the side in question expands less than the other, the 
normal respiratory murmurs are diminished on this side, and 
a stridor, caused by the stenosis, is heard. The breathing may 
become labored, but usually it does not assume the slow rhythm 
so characteristic of tracheal stenosis, probably because the 
respiratory rate is governed by the healthy lung. 

When any stenosis develops slowly, the patient learns to 
husband the oxygen which he receives by carrying out move- 
ments with the least possible exertion. In this way a man may 
work, even though the respiratory capabilities of his lungs 
have become far less than normal. 

The large bronchi may be narrowed by many of the causes 
which lead to stenosis of the trachea; as, for example, by 
tumors or cicatrices within, or by tumors or aneurisms press- 
ing upon them from without. On account of the large caliber 
of these tubes, a swelling of the mucous membrane does not 
ordinarily obstruct the passage of air. In the case of the 
smaller bronchi, however, the most frequent cause of obstruc- 
tion is just such an inflammation of the lining mucous mem- 
brane. If only the larger bronchi are involved in a bronchitis, 
little effect, therefore, is produced upon the interchange of 
gases in the lungs; whereas, if the smaller tubes become in- 
flamed, the results are far more serious. This is especially 
true of children, on account of the small size of their air- 
passages, and is also true of those who have scoliosis, for 
their pulmonary surface is already reduced from that cause. 

In every severe bronchitis the respiratory rate is increased, 
and sixty or eighty per minute, or even more, is not uncommon. 
At the same time, the respirations become more shallow. The 
rate is usually faster when the patient has fever, for fever 
itself accelerates the breathing. We are quite ignorant as to 
the cause of the characteristic breathing of bronchitis and 



206 CLINICAL PATHOLOGY 

especially of the cause of its shallowness. A mere retention 
of carbon dioxide in the blood will not produce this effect. 
Possibly the accumulation of this gas in the pulmonary alveoli, 
or the inflammation as such, stimulates the vagus endings in 
some peculiar way ; but of this there is no direct proof. 

Bronchial Asthma. — The symptoms of bronchial asthma 
are probably caused by a general narrowing of the bronchi, 
and they may therefore be discussed in this connection. The 
violent paroxysms of dyspnoea, which characterize asthma, 
usually begin at night, independently of circulatory conditions, 
and usually last hours or days. Inspiration and expiration are 
both labored, but expiration is especially interfered with. 
There is usually some cyanosis and inspiratory retraction of 
the soft tissues about the chest. During the paroxysm, the 
lungs rapidly increase in volume until they attain their maxi- 
mum expansion, such as is present normally only on deepest 
inspiration. Numerous musical rales, caused by the passage 
of air through the narrowed tubules, are heard over the lungs. 
In the earlier stages of the disease, the patient usually feels well 
between the attacks, but later he is apt to suffer from bronchial 
catarrh, cough, and at times from continual dyspnoea. 

Asthma is frequently associated with diseases of the 
bronchi, especially with that condition described by Cursch- 
mann as bronchiolitis exudativa chronica, which is character- 
ized by a tough and mucinous sputum, containing spirals and 
Charcot-Leyden crystals. The chemical investigation of the 
asthmatic sputum lends support to the view that it is essentially 
an anomaly of secretion rather than a true inflammatory exu- 
date. 7 Some believe that asthma may follow the ordinary 
bronchitis of pulmonary emphysema, but this view is not well 
substantiated. It is often difficult in these cases to determine 
whether the emphysema or the asthma is primary; but it 

7 F. Muller, Sitzber. d. Gesell. zur Befor. der ges. Naturwissensch., 
Marburg, 1896, No. 6. 



THE RESPIRATION 207 

usually seems to be the latter. Asthmatic attacks have been 
frequently observed in association with diseases of the nose, 
such as polyps and swellings of the mucous membrane covering 
the turbinated bones and the septum. Possibly these nasal 
conditions are related in some way to the bronchiolitis exuda- 
tiva. Both may occur and improve together, yet not every case 
of asthma that is caused by nasal reflexes is accompanied by 
this peculiar change in the bronchioles. Reflexes from other 
portions of the respiratory tract, and even from other organs, 
may precipitate the asthmatic paroxysm, but in the majority 
of these cases a bronchiolitis exudativa is present. 

Since asthma may be produced by such different causes, it 
seems doubtful if all cases are really of the same nature. In 
the great majority, a bronchiolitis is present, and these cases, 
at least, can be grouped together for consideration. As to the 
cause of the hinderance to the entrance and, especially, to the 
exit of air, the first theory which suggests itself is that the 
obstruction is due to the swelling of the mucous membrane 
and to the abnormal secretion of mucus. 8 It seems to us, 
however, improbable that these could produce an obstruction 
so rapidly as it occurs in asthma, and we know, furthermore, 
that an ordinary catarrh of the finer bronchi produces quite a 
different clinical picture. 

The asthmatic paroxysm seems to be rather of a spasmodic 
character. Two theories have been advanced as to the location 
of the asthmatic spasm. According to one, asthma is due to a 
spasm of the diaphragm, induced by a stimulation of the vagus 
nerve. 9 Such an explanation would account for the great 
distention of the lungs, but it leaves unexplained the inspiratory 
retraction of the soft tissues about the thorax and the presence 
of the sibilant rales. Furthermore, it is extremely improbable 
that the diaphragm, a voluntary muscle, should be able to 

8 Ungar, Kongr. f. in. Med., 1885, p. 245. 
Riegel, ibid., p. 250. 



208 CLINICAL PATHOLOGY 

remain in a state of tonic contraction for hours at a time with- 
out tiring. 

According to the other theory, the spasm affects the muscles 
of the smaller bronchi; and this seems more probable, for it 
has been demonstrated experimentally that a spasm of these 
muscles will give rise to all the symptoms of asthma. 10 In 
addition to this spasm, there may be present a catarrhal or 
hyperaemic swelling of the bronchial mucous membrane. It 
is not yet certain just how great a role such spasms of the 
bronchioles actually play in the production of the asthmatic 
attacks in man, and just what part may be played by contrac- 
tions of the diaphragm. 

The attacks may certainly be initiated through reflex in- 
fluences ; arising, most frequently, from sensitive parts of the 
respiratory tract, such as the turbinates of the nose and the 
surfaces of the finer bronchi. The nature of the primary 
irritant which gives rise to the reflex and the cause of the 
increased sensitiveness of the points from which the reflex 
starts are alike unknown to us. For a long time there was 
a tendency to regard the Charcot-Leyden crystals of the spu- 
tum as the primary irritants, but they have since been found 
in many other conditions. 

Paralysis of the Respiratory Muscles. — The aeration of 
the lungs suffers if the thorax or the lungs cannot sufficiently 
expand and contract. A mere rigidity of the chest wall usually 
does little harm, for, by increasing the movements of the 
thorax as a whole, and of the diaphragm, the lungs may be 
moved sufficiently to keep them aerated. 

More serious consequences result from weakness of the 
respiratory muscles. These latter may be affected directly as 
in general muscular atrophy or trichinosis; or they may be 
paralyzed in various diseases of the nervous system. The 

10 Gerlach, Pfliiger's Arch., vol. xiii. p. 491 ; Einthoven, ibid., vol. li. 
P- 367. 



THE RESPIRATION 209 

diaphragm and the other muscles of respiration may be para- 
lyzed together or separately. Extraneous conditions frequently 
interfere very seriously with the diaphragmatic movements; 
such as, for example, pleurisy, peritonitis, and abdominal dis- 
tention, whether from fluid, gas, or a tumor. These latter 
conditions interfere with the respiration by forcing the dia- 
phragm up and by offering an abnormal resistance to its in- 
spiratory descent. 

The disturbance of respiratory function from these various 
causes is intimately dependent upon the extent and the loca- 
tion of the disease. A destruction of all inspiratory muscles 
is quickly fatal. Of the more limited diseases, the most dan- 
gerous is bilateral paralysis of the diaphragm, which may be 
caused by disease of both phrenic nerves. This condition is 
also always fatal. A less serious paralysis may not cause 
death, but merely interfere with the interchange of gases in 
the lungs. The respiratory muscles remaining unparalyzed 
are then stimulated to increased exertion, and this may give 
rise to some unusual type of respiration, such as a pure costal 
type in a man, etc. ; and not only the type, but also the rate 
of the respirations may be changed. 

Loss of Pulmonary Elasticity. Emphysema. — As has 
been mentioned already, the elasticity of the lungs plays an 
important role in normal respiration, for it is one of the main 
factors in forcing the air out during expiration. If the lungs 
are greatly over-distended, or if their tissue suffers alteration 
in certain other ways, then their elasticity — i.e., their tendency 
to collapse — is more or less lost. Such a loss of elasticity of 
the whole or of a part of the lungs may result from many 
causes, such as diseases associated with violent inspirations or 
coughing, or those in which the exit of air from the lungs is 
obstructed, i f a large portion of the lungs has lost its elasticity 
from over-distention, respiration becomes difficult; for the 
distended lung does not exhibit the normal tendency to col- 

M 



210 CLINICAL PATHOLOGY 

lapse on expiration, and, not being fully collapsed, it cannot 
expand so well on inspiration. For this reason the functional 
capacity of the inelastic lung remains less than normal, even 
after the primary cause of the over-distention has ceased to 
act. 

Emphysema of the lungs diminishes the pulmonary elas- 
ticity. This is serious, because the emphysema is irreparable 
and lasts throughout life, and especially because it causes, in 
addition, an actual loss of lung substance. Many alveolar septa 
disappear during the disease, and the total functioning surface 
of the lungs is markedly contracted. The loss of the septa 
leads to an obliteration of many pulmonary capillaries, and 
so increases the resistance to the flow of blood through the 
lungs. For this reason hypertrophy of the right ventricle and 
accentuation of the second pulmonic sound are common findings 
in emphysema. Emphysema is usually unevenly distributed 
throughout the lungs, the free margins in front being most 
affected. 

Emphysema tends especially to develop in those whose 
pulmonary tissues have been exposed to injuries, such as are 
produced by asthma and bronchitis. Yet not all patients 
suffering from these diseases become affected with emphysema ; 
and, furthermore, the condition may develop in individuals 
who have not apparently been exposed to any injurious agents. 
There seems, therefore, to be some special abnormality in the 
lungs of susceptible individuals, which either reduces their 
resistance to injurious agents, or allows spontaneous degenera- 
tion to take place. Whether these abnormalities are of a 
chemical or of a structural nature is uncertain. Virchow 
believed that, since the emphysematous portions of a lung are 
poor in pigment, the disease must have originated in many 
cases before the fifth year of life. 

Emphysema interferes with the interchange of gases in 
the lungs by decreasing both their elasticity and their func- 



THE RESPIRATION 211 

tioning respiratory surface. Consequently, the carbon dioxide 
escapes less readily from the blood, and, being retained in 
the body, it stimulates the respiratory centre in the medulla, 
thus causing stronger and perhaps more frequent respirations. 
The bronchitis that so often complicates emphysema likewise 
tends to accelerate the breathing. The deeper and more fre- 
quent respirations may to a certain degree neutralize the ill 
effects of the loss of elasticity. 

Respiratory Changes of Nervous Origin. The Cheyne- 
Stokes Phenomenon. — Changes in the activity of the respira- 
tory centre may directly influence the amounts of air which 
pass in and out of the lungs. Thus, when the intracranial 
pressure is increased, the respirations usually become slower 
and deeper, and frequently also more irregular. Anatomical 
lesions that injure, without destroying, the respiratory centre 
may give rise to similar effects. 

The peculiar type of breathing known as the Cheyne- 
Stokes respiration may be considered in this place. 11 In this 
condition the respiratory rhythm is broken by pauses of apncea. 
After one of these pauses, the respirations are at first weak 
and superficial, but gradually they become stronger and 
stronger, until they are exceedingly labored. Following this 
extreme dyspnoea, the respirations gradually diminish in 
strength until they cease altogether in the period of apncea, 
and the cycle of events is completed. Nervous symptoms 
frequently accompany the respiratory changes. The patient 
may lie in a stupor during the apncea, to awake during the 
period of dyspnoea with oppressive sensations. The pupils 
may be contracted and reactionless during the apncea, but 
become dilated and mobile during the dyspnoea. According 
to Traube, the pulse usually remains unaffected by the varia- 

11 Traube, Bcitr., ii. p. 882 and iii. p. 103 ; Sokolow and Luchinger, 
Pflugcr's Arch., vol. xxiii. p. 283; Luwit, Prag. mcd. Wochens., 1880, Nos. 
47-50; Unverricht, Kongr. f. in. Med., 1892, p. 399. 



212 CLINICAL PATHOLOGY 

tions in the breathing, though it may show definite changes in 
frequency and tension. Of the various causes which may pro- 
duce a Cheyne-Stokes type of respiration, the most important 
are uraemia and diseases of the brain and heart. 

The cause of this symptom-complex is believed to be 
some change in the irritability of the respiratory centre. 
Filehne 12 held that Cheyne-Stokes breathing is due to a rela- 
tive insensitiveness of this centre to the action of venous 
blood. For this reason the accumulation of carbon dioxide 
in the body does not affect the respiratory centre readily, and 
it is only after the venous blood has stimulated the vasomotor 
centre, and so has caused a constriction of the arteries leading 
to the brain, that the respiratory centre is finally influenced by 
the small amount and poor quality of the blood which it 
receives. The breathing then gradually deepens, and the 
blood becomes better aerated. The vasomotor centre, being 
no longer stimulated by venous blood, allows the arteries to 
dilate, and thus a fresh supply of arterial blood reaches the 
respiratory centre. The latter is then no longer stimulated 
by an insufficient blood-supply, and the animal stops breathing. 
Thus the cycle is completed and a new one can begin. This 
theory has been sharply attacked, especially by Rosenbach, who 
believes that the venous quality of the blood does not cause 
the Cheyne-Stokes phenomenon. 13 It is impossible to discuss 
the various explanations given for this type of breathing, 
mainly because so few facts are known to us. It should, 
however, be remembered that even in healthy individuals there 
is a tendency to periodic breathing, which is most marked 
during sleep, and that many animals always show this type of 
respiration. Of special interest is the theory of Unverricht, 14 

12 Arch. f. exp. Path., vol. x. p. 442, and vol. xi. p. 45 ; Ztft. f. klin. 
Med., vol. ii. p. 255. 

"Ztft. f. klin. Med., vol. i. p. 583, and vol. ii. p. 713. 
" Kongr. f. in. Med., 1892, p. 399. 



THE RESPIRATION 213 

who held that the phenomenon is due to some disturbance in 
the nervous paths connecting the cortex and the respiratory 
centre in the medulla. 

Changes in the respiratory centre are probably responsible 
for the abnormal breathing seen in certain intoxications ; such, 
for example, as the spasmodic breathing of hydrocyanic acid 
poisoning, or the deep respirations of diabetes, uraemia, and 
other conditions. 15 The frequent and superficial respirations 
of salicylic acid poisoning and the various forms of dyspnoea 
which may be present in hysteria also seem to be due to nervous 
influences. 

The respiratory centre may be affected by reflexes from 
various parts of the body, especially from the abdominal 
organs. The conditions known as asthma dyspepticum, 16 
asthma uterinum, etc., are caused in this manner. 

Pleural Effusions and Pneumothorax. — Even though the 
movements of the chest are normal, and the air can reach the 
alveoli, respiratory difficulties may arise from a diminution of 
the total functionating pulmonary surface. Such a diminution 
may be caused by numerous diseases, either because they fill 
the alveoli with inflammatory products, as happens in pneu- 
monia, or because they obliterate them by pressure from 
without, as happens in large pleural exudates. 

When fluid collects in the pleural cavity, the lung at first 
retracts in virtue of its elasticity, but later it is pressed upon 
by the fluid, and it may be entirely emptied of air by very 
large effusions. A pleural effusion does harm in several ways. 
In the first place, the retraction and compression of the lung 
on the side of the fluid naturally diminishes the surface avail- 
able for the interchange of gases. Since the pressure in the 
diseased pleural cavity is higher than that in the healthy cavity, 

" Kussmaul, Arch. f. klin. Med., vol. xiv. p. I ; Senator, Ztft. f. klin. 
Med., vol. vii. p. 235. 

19 Boas, Arch. f. Verdauungstr., vol. ii. p. 345. 



214 CLINICAL PATHOLOGY 

the fluid tends to force the mediastinum toward the healthy 
side, and so to interfere not only with the function of the 
lung on the affected side, but with that on the healthy side as 
well. A pleural effusion also influences the circulation of the 
blood. The negative pressure, normally present in the thorax, 
is diminished, and the venous flow from the periphery toward 
the heart is consequently retarded. Large exudates may even 
compress or kink the inferior vena cava. The increased press- 
ure upon the capillaries of the lungs raises the resistance in 
the pulmonary circulation, and thus increases the work of 
the right ventricle. 

If air escape into the pleural cavity through a wound in the 
chest wall, or through an opening in a lung produced by such 
causes as tuberculosis, abscess, gangrene, or injury, it gives 
rise to many of the same results as does an effusion. When 
such a pneumothorax communicates freely with the external 
air, the pressure in the affected cavity will be the atmospheric 
pressure. If, however, the opening becomes completely closed, 
then a part of the air in the pleural cavity is absorbed, and 
the pressure in this cavity, though less than that of the atmos- 
phere, remains greater than that on the normal side. If, 
finally, the opening be of a valvular nature, such that it will 
permit air to enter the pleural cavity, but will prevent its exit, 
then the pressure within will exceed the atmospheric pressure, 
at least during rest and expiration, and not only the lung of 
the affected side, but that of the other side also, will be sub- 
jected to considerable pressure. 

The seriousness of a pneumothorax depends mainly upon 
the functional capacity of the healthy lung. If this can func- 
tionate without interference, all the demands of the resting 
body may be met, even though the pneumothorax should 
have developed suddenly. Unfortunately, the healthy lung is 
often encroached upon by the mediastinum, owing to the fact 
that the latter is thrust past the median line by the high 



THE RESPIRATION 215 

pressure in the affected cavity. 17 When the opening into 
the pleural cavity is a large one, and admits of free commu- 
nication with the external air, then with each inspiration the 
mediastinum is displayed toward the healthy side, and the 
air does not enter the normal lung so well as normally. Less 
effect is produced if the mediastinum is very rigid or if the 
opening into the pleural cavity is a small one. The severe 
collapse which sometimes follows a large perforation into the 
pleural cavity, may be overcome experimentally by preventing 
this displacement of the mediastinum. In general, a right- 
sided pneumothorax is more serious than a left-sided one, 
because of the greater capacity of the right lung. 

Atelectasis. — An inflammation of the smaller bronchi may 
decrease the respiratory surface of the lungs, for when the 
bronchioles are occluded by a swelling of the mucous mem- 
brane, the corresponding alveoli are rendered useless. If the 
occlusion persists for a long time, the air contained in the 
affected air-cells gradually undergoes absorption and the cor- 
responding pulmonary tissues become atelectatic. 18 The oxy- 
gen and carbonic acid gas are rapidly absorbed, the nitrogen 
more slowly. The gases are absorbed because the alveoli tend 
to contract, and in this manner they keep the partial pressure 
of the various gases within them at a higher level than the 
partial pressure of these same gases in the blood. 

Atelectasis may also be caused by compression of the lungs, 
as from large pleural effusions or pneumothorax. According 
to Lichtheim, it is possible for the alveoli to become atelectatic, 
even though there is no occlusion of the bronchi and no actual 
compression. For example, the portion of the lung which 
dips into the fluid of a small pleural exudate is not subjected 
to a positive pressure, and yet it is usually found to be free 
of air. 

17 See Garre-Quincke, Grundriss dcr Lungenchirurgie, Jena, 1903, p. 40. 
"Lichtheim, Arch f. exp. Path., vol. x. p. 54. 



216 CLINICAL PATHOLOGY 

The Effects of an Obliteration of the Air-Spaces. — The 
disturbances produced by a diminution of the functioning 
surface of the lungs depend upon several factors, such as the 
amount of pulmonary tissue thrown out of function, the 
rapidity with which this occurs, the demands of the body for 
fresh oxygen, and the degree to which an increase in the 
respiratory movements can compensate for the loss of func- 
tioning tissue. 

Such a diminution in the functional capacity of the lungs 
always causes a deepening of the respirations, and frequently 
an increase in their rate as well. The latter is especially marked 
when fever is present, for the heated blood seems to stimulate 
the respiratory centre not only directly, but through reflexes 
from the skin. Even though there be no fever, the respira- 
tions may be accelerated. One probable cause for the increased 
respiratory movements in these conditions is the stimulation of 
the respiratory centre by the carbon dioxide retained in the 
blood, though it must be admitted that we possess no positive 
data actually proving that such a retention takes place in 
cases of atelectasis. The breathing may also be accelerated 
from another cause. The inspiratory movements enlarge the 
chest cavity, and, since many alveoli involved in the atelec- 
tasis do not expand, the remaining ones must expand all the 
more. This excessive distention of certain alveoli probably 
stimulates the vagus nerve, thus rendering the succeeding 
expiration prompt and forcible, and perhaps increasing the 
respiratory rate. This is a possible explanation of the rapid 
respirations so frequently seen in cases of atelectasis without 
fever. 

Disturbances in the interchange of gases in the lungs may 
arise from changes in the chemical or physical character of 
the alveolar membranes. Of this we have no direct experi- 
mental proof, but a priori it would seem possible, and the 
dyspnoea of patients who suffer from chronic passive conges- 



THE RESPIRATION 217 

tion, consecutive to heart disease, is partially accounted for by 
changes in the alveolar epithelium. 

The Effects of Atmospheric Pressure upon Respiration. — 
Variations in the composition of the air must produce certain 
effects upon the animal organism, for the passage of the gases 
through the alveolar membranes depends primarily upon the 
relation existing between the partial pressures of these gases 
in the blood and in the air-cells. The partial pressure of 
oxygen in the lungs may be diminished either by diminishing 
the atmospheric pressure as a whole or by diminishing the 
relative proportion of oxygen in ordinary air. Practically, 
the latter is seen only when an animal is allowed to breathe 
in a small air-tight space until the oxygen is reduced. The 
symptoms produced are those of asphyxia, and will be spoken 
of in that connection (p. 225). 

The effects of low atmospheric pressure are frequently 
seen, 19 especially in those who make balloon ascensions and in 
those who reach great heights in mountain climbing. The 
symptoms may be merely unpleasant at first, but at higher 
elevations they become actually dangerous. The height at 
which symptoms develop varies for different individuals and 
under different conditions. Dyspnoea, headache, prostration, 
paralysis of the extremities, and finally complete unconscious- 
ness are among the symptoms which may appear during a 
balloon ascension, and a similar set of symptoms — viz., fatigue, 
headache, sleepiness, palpitation, nausea, rapid pulse and respi- 
ration, and especially dyspnoea — may also harass those who 
ascend high mountains. In both instances the symptoms are 
not caused by the reduction of atmospheric pressure alone, 
but are due in part to the cold, the wind, the dazzling light, 
and the bodily and mental strain. Unquestionably, however, 
the rarefied air is the main cause of the disturbances, even in 

"Miescher, Arch. f. exp. Path., vol. xxxix. p. 464; Kronecker, Die 
Bergkrankheit, Berlin, 1903. 



218 CLINICAL PATHOLOGY 

mountain climbing, for the symptoms can appear in persons 
who do not climb but are carried up the mountain. 20 

A considerable rarefaction of the respired air may take 
place without any resulting disturbance in the interchange of 
gases in the lungs. Most animals and men will endure, with- 
out serious consequences, a reduction of the atmospheric press- 
ure from the normal of 760 mm. down to 450 or 400 mm. of 
mercury, and some will stand a reduction to half an atmosphere 
or less. The manner in which the individual breathes is of 
great importance in determining his ability to withstand these 
reductions of pressure. Those that are accustomed to keep 
their lungs well ventilated with fresh air resist a lowering of 
pressure comparatively well, for they know how to keep the 
partial pressure of oxygen in their alveoli at a relatively high 
level. Anything that acts unfavorably upon the mechanics of 
respiration, such as cold, wind, loss of sleep, etc., renders the 
individual more susceptible to a diminution in atmospheric 
pressure. For these reasons there are great individual varia- 
tions in the ability to withstand low atmospheric pressures, and 
animals, as well as men, living at high altitudes gradually learn 
to breathe in such a manner that the partial pressure of the 
oxygen in their alveoli shall be maintained at a comparatively 
high level. 

According to certain observers, 21 the interchange of gases 
in the lungs is not affected until the pressure of the external 
air reaches about half an atmosphere. If the pressure be 
reduced beyond this, then the elimination of carbon dioxide is 
markedly increased and the absorption of oxygen is likewise 
somewhat increased, though relatively less so, at least in the 
early stages. Observations by Zuntz, extending over several 

20 Egli-Sinclair, Wien. med. Blatter, 1895, 8 and 9. 

21 Fraenkel and Geppert, Ueber die Wirkungen d. verdiinn. Luft auf 
d. Organismus, Berlin; Loewy, Unters. u. Resp. u. Circ, etc., Berlin, 
i895- 



THE RESPIRATION 219 

weeks, upon persons at the top of Monta Rosa ( four thousand 
five hundred metres high), showed a considerable increase in 
the respiratory movements and in the consumption of oxy- 
gen, though the amount of this increase differed in differ- 
ent individuals. The persons subjected to these last experi- 
ments did not seem to become acclimated to the changed 
conditions within the short time that they remained at the 
high altitude. 

The oxygen-carrying capacity of the haemoglobin does not 
diminish at the same rate as does the partial pressure of the 
oxygen to which it is exposed. Thus Hiifner 22 has shown 
that with the partial pressure of oxygen at 124 mm. (corre- 
sponding to an elevation of two thousand metres), ninety 
per cent, of the haemoglobin remains undecomposed, at a 
partial pressure corresponding to an elevation of four thousand 
metres, eighty-eight per cent., and at one corresponding to six 
thousand metres, eighty-five per cent., remain undecomposed. 
The dissociation of oxyhaemoglobin may therefore be rela- 
tively slight at these high altitudes, and it is to this fact that 
the animal body owes its considerable ability to resist reduc- 
tions of pressure. Yet we must remember that the partial 
pressure of the oxygen in the lungs may be considerably lower 
than is its partial pressure in the outside air. As the blood 
becomes insufficiently aerated, the respiratory movements are 
increased and the partial pressure of the oxygen in the alveoli 
is raised. This constitutes a most important mechanism, 
whereby the body is able to compensate for reductions of 
atmospheric pressure. Muscular exercise sometimes relieves 
the unpleasant symptoms of a rarefied atmosphere, probably 
because it stimulates the respiratory movements. 

In conclusion, we may say that the effects of a high altitude 
.are caused mainly by the diminution in the tension of the 
oxygen, and to a lesser extent by other causes. The condi- 

"Englemann's Arch., [901, p. 187. 



220 CLINICAL PATHOLOGY 

tions are very complicated, and it must be acknowledged 23 
that various factors, such as circulatory disturbances, for 
example, may contribute to the production of symptoms. Yet, 
in my opinion, the lack of oxygen is the essential cause, and 
this view is supported especially by the fact that the symptoms 
of those who ascend to great elevations in balloons are often 
promptly relieved by inhalations of oxygen. 

Increasing the density of the air even up to twice the normal 
pressure is, according to recent observations, 24 without any 
effect upon the " quality or quantity" of the respiratory inter- 
change of gases. The increased appetite and the loss of weight 
that are seen in persons subjected to high pressures cannot 
therefore be accounted for by any anomalies in the respiration. 

The Inhalation of Poisonous Gases. — The respired air 
may contain substances which are poisonous to the body. A 
certain protection from these poisonous admixtures is furnished 
by our sense of smell, and some gases, such as ammonia and 
sulphuretted hydrogen, are avoided on account of their odors. 
Yet the odor of hydrocyanic acid may be perceived only after 
it is too late to escape its deadly action. 

Carbon monoxide, as usually inhaled, is mixed with gases 
which possess an odor. Poisoning from this gas is of especial 
interest, on account of the marked affinity which it possesses 
for haemoglobin. 25 When the air contains about one part in 
a thousand of carbon monoxide,- the latter passes into the blood, 
where it unites with a portion of the haemoglobin in such a 
manner that this latter can no longer combine with oxygen 
to form oxyhemoglobin. If only a small amount of haemo- 
globin is thus thrown out of function, no serious damage 



23 Kronecker, Die Bergkrankheit, Berlin, 1903. 

24 Loewy, loc. cit. 

25 Hufner, Arch. f. exp. Path., vol. xlviii. p. 87 ; Mosso, Die Atmung 
in d. Tunnels u. d. Wirkunk d. Kohlenoxyds, see Jahresber. f. Tierchemie, 
vol. xxx. p. 576. 



THE RESPIRATION 221 

results, and the patient has only a few symptoms, such as 
headache, etc. If he then breathes good air, the changed 
haemoglobin is either excreted, or the combination between it 
and the carbon monoxide is gradually decomposed by the mass 
action of fresh oxygen. When, however, large quantities of 
• haemoglobin are thus thrown out of function, the blood can no 
longer furnish the necessary oxygen to the body. 26 Under 
such circumstances, the carbon dioxide is excreted through the 
lungs as usual, but the supply of oxygen is diminished, and 
this becomes dangerous as soon as about fifty per cent, of the 
total haemoglobin is decomposed. In rabbits killed by carbon 
monoxide only twenty to thirty per cent, of the normal amount 
of oxygen was found in the blood at the time of death. Part 
of the carbon monoxide in the blood passes into the tissues, 
and there exerts its anaesthetic action. Consequently the respi- 
rations early become paralyzed, and the clinical picture pre- 
sented differs entirely from that of acute asphyxia. If the 
poisoned person be removed from the gas, and if he breathe 
ordinary air, or, better still, pure oxygen, then the combination 
between the carbon monoxide and the haemoblobin is gradually 
decomposed and he may be saved. 27 

The Effects of Anaemia upon Respiration. — The supply of 
oxygen to the tissues may be influenced by a reduction of 
haemoglobin. If there be too small a quantity of this pigment 
in the circulating blood, or if that present be transformed into 
some useless modification, such as the carbon monoxide com- 
pound or methaemoglobin, then the supply of oxygen to the 
body may become insufficient. In an acute hemorrhage death 
results from this cause when about seventy per cent, of the 
total quanity of haemoglobin is lost. 

If the loss of haemoglobin or of blood be very gradual, then 
the body learns to accustom itself to the changed conditions, 

^Dreser, Arch. f. cxp. Path., vol. xxlx. p. 119. 
27 Grehant, compt. rend., vol. cii. p. 825. 



222 CLINICAL PATHOLOGY 

and a much greater reduction can take place. We do not 
know the limits to which such a gradual reduction of the total 
haemoglobin may go, for we have no method for accurately- 
determining the total quantity of blood in the body. Nor do 
we fully understand the manner in which the body accom- 
modates itself to a gradual loss of haemoglobin. It is certain 
that there is no modification of the haemoglobin itself in these 
cases, whereby it is enabled to transport larger quantities of 
oxygen. 28 Furthermore, the total amount of oxygen absorbed 
and of carbon dioxide eliminated during rest are little if any 
below the normal limits, even though the anaemia be severe. 29 
Such patients learn to restrict their movements as much as 
possible, and so to lessen their need for oxygen ; and although 
the quantity of oxygen which they consume during rest is the 
same as that used by a healthy individual, yet their gaseous 
interchange during exercise is much less than normal. 30 Then 
it is that their lessened facilities for transporting oxygen are 
most noticeable, and every physician knows how incapable of 
exertion these anaemic persons are. 

Since in an anaemic person a small amount of haemoglobin 
must supply the tissues with the usual amount of oxygen, at 
least during rest, it follows that either the haemoglobin present 
makes more frequent journeys from the lungs to the tissues, 
or that it gives up more oxygen to the tissues at each journey. 
We possess no evidence proving that the blood-flow is in- 
creased in anaemia, though the rapid heart action so frequently 
observed does perhaps tend to produce this result. It is much 
more probable that the oxyhemoglobin of the blood is more 
reduced in the tissues of an anaemic than in those of a healthy 

2s Hiifner, Englemann's Arch., 1900, p. 39; ibid., 1903, p. 217. 

20 Pettenkofer and Voit, Ztft. f. Biol., vol. v. p. 419 ; Pembry and 
Gurber, Jour, of Physiol., vol. xv. p. 449; Thiele and Nehring, Ztft. f. 
klin. Med., vol. xxx. p. 41. 

80 Kraus, Ztft. f. klin. Med., vol. xxii. pp. 449, 574. 



THE RESPIRATION 223 

individual, and that, correspondingly, a given amount of 
haemoglobin must take up relatively more oxygen in the lungs. 
The absorption of oxygen from the alveoli is favored by the 
fact that anaemic persons, by virtue of their increased respira- 
tory movements, usually keep their lungs better aerated than 
do normal individuals. Consequently the partial pressure of 
the oxygen in the blood of anaemic persons, though less than 
the normal, is yet sufficient to meet the needs of the body. 

The Effect of Circulatory Changes upon the Respiration. 
— If the body is to receive a proper supply of oxygen, it is 
not only necessary that there should be sufficient air in the 
lungs and sufficient haemoglobin in the blood, but there must 
also be a sufficiently rapid blood-stream. The haemoglobin 
takes up the oxygen from alveolar spaces very rapidly, and no 
advantage, therefore, is derived from a slowing of the blood- 
current through the lungs. When, however, the rapidity of 
the blood-current is so diminished that the respiratory centre 
is not sufficiently aerated, then the cells in the medulla are 
stimulated and the respiratory movements are deepened. These 
increased respiratory movements are of special value in circu- 
latory disturbances because they not only maintain the partial 
pressure of the oxygen in the alveoli at a higher level, but 
they directly assist the flow of blood. 

Respiratory Compensation. — We see, therefore, that con- 
ditions which injure the external respiration call into play 
compensatory processes by means of which the body endeavors 
to protect itself against the harmful effects of a lessened in- 
ternal respiration. To what extent it is possible to do this 
depends upon various factors. In the first place, it depends 
upon the degree to which the external respiration is disturbed, 
and it is clear, for example, that no compensation can possibly 
help a patient if an aortic aneurism ruptures and fills all the 
alveoli of his lungs with blood. Secondly, it depends upon 
the functional capacity of the compensatory organs, and a 



224 CLINICAL PATHOLOGY 

movable chest wall, good muscles, and a powerful heart are 
most important aids to compensation. Thirdly, it depends upon 
the respiratory needs of the body. Compensation is more 
easily maintained when the body is at rest than when the 
demand for oxygen is increased by exercise or during digestion. 
Finally, the rapidity of the changes is important and com- 
pensation is more easily established when the damage develops 
gradually; for persons with disturbances of respiration learn 
in time to minimize their need of oxygen. We have already 
mentioned the manner whereby the interchange of gases is 
approximated to the normal in anaemia. The same has also 
been studied in certain other pathological conditions. It has 
been shown, for example, that in rabbits a pleuritic exudate or 
a closed pneumothorax of moderate grade does not influence 
to any marked degree the quantity of oxygen absorbed or that 
of carbon dioxide eliminated by the lungs. 31 An open pneu- 
mothorax of one side produces equally little disturbance in 
rabbits and dogs. 32 In man, also, the effect of various diseases 
upon the interchange of gases has been studied by accurate 
methods. In emphysema, bronchitis, tuberculosis, pneumonia, 
and pleurisy, even when marked dyspnoea was present, the 
interchange between the lungs and the external air was found 
to be approximately normal. Yet when there is dyspnoea, 
additional oxygen is used up by the increased respiratory 
movements ; and, if this were deducted from the total amount 
of oxygen consumed by such patients, there might prove after 
all to be some reduction in their interchange of gases. The 
latter seems all the more probable from the fact that the 
respiratory interchange of gases in the above conditions tends 
to diminish as the hinderance to the entrance of air increases. 
Yet even though the external respiration were apparently 
unaffected, we must be careful not to assume that the respira- 

31 Thoma and Weil, Virch. Arch., vol. lxxv. p. 483. 

32 Sackur, Ztft. f. klin. Med., vol. xxix. p. 25. 



THE RESPIRATION 225 

tory processes within the body are normal; for it is possible 
that the tension of the oxygen in the blood might be abnor- 
mally low or that of the carbon dioxide abnormally high. 
Either would influence the interchange of gases between the 
blood and the tissues. Indeed, dyspnoea is usually caused by 
just such changes in the blood going to the medulla. 

Asphyxia. — When disturbances of external respiration be- 
come considerably greater than can be met by the compen- 
satory mechanism, asphyxia is produced. The symptoms of 
asphyxia vary according to the rapidity of its onset, being 
milder and less characteristic in gradually progressive cases. 
The blood is altered in two particulars in asphyxia, there being, 
first, a diminution in quantity of oxygen present, and secondly, 
an increase in the carbonic acid gas. The latter possesses some 
anaesthetic action, and consequently, when it acts over a long 
period of time, as in chronic asphyxia, the irritability of the 
medulla gradually becomes diminished and the respirations 
may weaken until life is extinct. In such conditions the effects 
of the lack of oxygen do not become apparent, because the 
'respiratory centre has been narcotized by the carbon dioxide. 

Acute asphyxia is produced by suddenly cutting off the 
oxygen supply to a brain which has not yet lost its irrita- 
bility. Practically, this does not happen very often, but may 
result from a filling of the lungs with fluid, from the collapse 
of a diseased trachea, or from a rapidly fatal hemorrhage. 
The lack of oxygen first causes a deepening and strengthening 
of the respirations, followed by characteristic changes in the 
circulation. The vasomotor centre is powerfully stimulated, 
and this causes the splanchnic vessels to contract, the vessels 
of the skin to dilate, and the general arterial pressure to be 
markedly raised. The vagus is also stimulated and the heart- 
rate is slowed. These changes result in a maximum amount 
of blood being sent to the brain so that the latter receives the 
best oxygen supply possible. In the later stages of acute 

15 



226 CLINICAL PATHOLOGY 

asphyxia generalized tonic and clonic convulsions occur, and 
finally, after a brief period of paralysis, death supervenes. 

The Internal Respiration. — The internal respiration has 
already been mentioned, and we have attempted to show how 
changes in the internal respiration of the respiratory centre 
may cause a compensatory increase in the movements of the 
chest. 

The effect of disturbances of the external respiration upon 
the interchange of gases in other tissues remains to be con- 
sidered. The need of the cells for oxygen is determined 
primarily by their functional activity, yet it must not be for- 
gotten that they cannot use all the oxygen they need unless 
it is properly furnished to them. It is, indeed, true that for a 
certain period of time the cells are able to do without fresh 
air, for the reason that they possess a supply of intramolecular 
oxygen; but this fact is of little practical importance. 

Normally the blood carries much more oxygen than is 
needed by the tissues, and when it leaves them its supply is 
by no means exhausted. We have evidence that this excess of 
oxygen is not a useless luxury, but that it is beneficial, and 
that a relative scarcity of the gas in the tissues is directly 
harmful. At least, it has been shown that in dyspnceic dogs 
the proteid decomposition is increased, 33 and, although the 
same has not been proved for man, it suggests the harm which 
may result from an insufficient aeration of the blood. It has 
been shown also that glucose and lactic acid may appear in the 
urine of dyspnceic animals, and that lactic acid may be present 
in the urine of dyspnceic men. 34 Finally, the ratio between the 
carbonic acid gas eliminated and the oxygen absorbed becomes 
greater than the normal ratio if the oxygen supply is re- 
stricted. Though the explanation of these various findings is 
uncertain, they serve to show that a diminished tension of 

33 Fraenkel, Virch. Arch., vol. lxvii. p. 273. 
31 Araki, Ztft. f. phys. Chem., vol. xv. p. 335. 



THE RESPIRATION 227 

oxygen in the tissues leads to pathological changes in the 
metabolism of the body. 

In order to estimate the oxygen supply to the tissues, it is 
necessary to know the amount of this gas in the blood. Un- 
fortunately, we possess but little information bearing directly 
upon this point. In animals with an open pneumothorax the 
quantity of oxygen is much diminished in the arterial blood, 
and it is this diminution that stimulates the medullary centres, 
causing such powerful respirations that one lung is able to do 
the work of two. 35 In the anaemias, also, the total amount 
of oxygen in the blood is reduced proportionally to the reduc- 
tion in haemoglobin. 36 We possess no other data as to the 
gases in the blood in respiratory diseases. The mere fact 
that the external interchange of gases with the air does not 
vary from the normal proves nothing, for this might be the 
same even though the absolute amount in the blood varied 
greatly, as, indeed, probably happens in anaemia and pneumo- 
thorax. The simple inspection of many patients with respira- 
tory diseases would lead one to the belief that their blood is 
poor in oxygen, because of the cyanosis present; and yet their 
consumption of oxygen is known to be approximately normal. 

If the oxygen in the blood is diminished, it is supplied to 
the tissue cells at an abnormally low tension. The amount of 
carbon dioxide in cyanotic blood is increased, and this will 
also produce some effect, for even in great dilution it stimu- 
lates the respiratory centre. 

Even though the lungs be normal, the internal respiration 
may be affected through changes in the parenchyma cells or 
in the tissue fluids. A retarded blood-flow or a lack of func- 
tioning haemoglobin interferes not only with the interchange 
of gases in the lungs, but likewise with the interchange in the 

"Sackur, Ztft. f. klin. Med., vol. xxix. p. 25. 

"Kossler and Scholz, Kongr. f. in. Med., 1899, p. 378; Arch. f. exp. 
Path., vol. xlii. p. 323. 



228 CLINICAL PATHOLOGY 

tissues. The slowing of the pulmonary bloocl-stream is of no 
advantage, for the red cells quickly become saturated with 
oxygen. The tissues may indeed abstract more oxygen from 
slowly moving blood, but this must be done under a lower mean 
pressure, and there is a limit beyond which the slowing of the 
current cannot go without reducing the oxygen supply to the 
tissues. 

Disturbances in the internal respiration may also be of a 
local nature, as when arteriosclerotic changes, thrombosis, or 
embolism interfere with the circulation of a limited portion 
of the body. If the cerebral arteries are blocked, the resulting 
anaemia of the brain produces the symptoms of acute asphyxia. 

The transportation of carbon dioxide may be interfered 
with by changes in the blood, especially those produced by 
an acid intoxication. The additional acid in such intoxications 
is partly neutralized by an increased formation of ammonia 
(see p. 337), yet not altogether so, and some of the fixed 
alkalies of the blood are bound by the extra acid. This dimin- 
ishes the free alkali in the blood which is available for carbon 
dioxide transportation, and, in rabbits, at least, the amount 
of carbon dioxide in the blood may be reduced from the normal 
twenty-five per cent, by volume, down to two per cent, as the 
result of an acid intoxication. 37 Under such circumstances, 
the plasma quickly becomes saturated with carbonic acid gas, 
and some of the latter is left to accumulate in the tissues. In 
the acid intoxication of rabbits, the oxidations in the body are 
also considerably diminished, 38 for the absorption of oxygen 
from the respired air is less than normal. Since the amount 
of oxygen in the blood is not lessened, 39 the decrease in the 
oxidative processes of the body must be referred to changes 

37 Walter, Arch. f. exp. Path., vol. vii. p. 148 ; H. Meyer, ibid., vol. 
xiv. p. 313. 

38 Chvostek, Ztrbl. f. klin. Med., vol. xiv. p. 329. 
30 Walter, loc. cit. 



THE RESPIRATION 229 

in the cells, induced, perhaps, by the toxic action of the re- 
tained carbon dioxide. Thus we see that in the acid intoxi- 
cation of rabbits the reduction of the fixed alkalies of the blood 
leads to disturbances both of internal and of external respi- 
ration. To what extent these results are applicable to the acid 
intoxications seen in man is not definitely known, for numer- 
ous other factors here present complicate the simple picture. 

The internal respiration may finally be altered by changes 
in the parenchyma cells, either physiological, such as by rest 
and activity, by cold and heat, or pathological, as by the 
various metabolic diseases. In phosphorus and hydrocyanic 
acid poisoning many cells lose to a greater or less extent their 
ability to take up oxygen and to form carbon dioxide. Though 
the external breathing and the gases of the blood are both 
normal, nevertheless the interchange of gases in the tissues 
is much diminished, because the cells are poisoned. The animal 
dies of internal asphyxia; and in hydrocyanic acid poisoning 
the most marked respiratory convulsive movements may result 
from this asphyxia of the respiratory centre. 

Respiratory Sensations. — The most important pathologi- 
cal sensation associated with respiration is that known as 
dyspnoea. The term has been used by some to designate dis- 
turbances in the respiratory act itself, but we prefer to limit its 
use to the subjective sensation of an air-hunger. Such a 
sensation is always produced by an insufficient interchange of 
gases in the tissues, especially by a diminution in the supply 
of oxygen to certain parts of the brain. The retention of 
carbon dioxide which is so frequently associated with the 
if oxygen does not apparently cause this sensation of air- 
hunger, for it may be breathed in large quantities without any 
such effect. Frequently the respiratory movements are in- 
creased without any sensations of dyspnoea, and it would seem 
that in such cases a retention of carbon dioxide is the important 
factor in producing the mere marked respiratory movements. 



230 CLINICAL PATHOLOGY 

How the oxygen is prevented from reaching the brain is 
immaterial, so far as dyspnoea is concerned; the respiratory 
surface of the lungs may be diminished, the blood may flow 
slowly, or, finally, either the red corpuscles or the tissue-cells 
may have lost their ability to take up the oxygen. The need 
for oxygen is increased by a functional activity of the cells of 
the body, and for this reason many patients are free from 
dyspnoea so long as they are quiet, but suffer from it so soon 
as they exert themselves. Many gradually learn to accomplish 
their tasks with a minimum expenditure of energy, and so to 
reduce their need of oxygen and their dyspnoea. 

Actual pain may be caused by diseases of the respiratory 
apparatus. Most authors believe that the lungs themselves 
contain no fibres which are capable of transmitting sensations 
of pain and that all pulmonary pains arise from the pleura or 
the chest wall. Severe pains are frequently present in dry 
pleurisies, and, since the latter often accompany diseases of 
the lungs, it is possible that they are responsible for the pain 
present in many of these cases. Yet the question is not, to 
my mind, fully settled, for pain may be present in diseases 
of the lungs which are not accompanied by pleurisy. 






CHAPTER VI. 



THE DIGESTION. 



The Mouth and CEsophagus. — Digestion includes all of 
the processes which assist in preparing the food for use in the 
body. Disturbances of digestion, therefore, begin in the mouth. 
Here the food is seized by the teeth and is ground up so that 
it shall present a greater surface to the action of the digestive 
juices. Serious disturbances may follow improper trituration 
of the food, whether this results from diseases of the teeth, 
the maxilary bones, or the temporo-maxillary joints, or from 
weakness of the muscles which move the food about within 
the mouth. If the facial nerves are paralyzed, the food col- 
lects in the cheeks and cannot be forced back into the mouth. 
A paralysis of the tongue interferes not only with chewing, 
but with the passage of food into the throat. When chewing 
becomes a painful procedure, malnutrition may be a conse- 
quence; for many patients with ulcerations in the mouth, or 
with inflammations of the tonsils, throat, or parotid glands, 
would rather suffer from hunger than from the pain which is 
caused by the taking of food. The intensity and the duration 
of such diseases both influence the amount of disturbance 
which they produce. 

Stomatitis. — The causes of stomatitis are various. If par- 
ticles of food are retained in the mouth, they decompose, and 
the products of decomposition, acting as irritants, may pave 
the way for the invasion of micro-organisms. Inflammations 
are also more liable to occur when the growth of bacteria is 
favored by carious teeth, or when, as the result of severe ill- 
nesses, but little saliva is secreted and the mouth is allowed 
to become foul owing to the stuporous condition of the patient. 
The stomatitis which so often accompanies severe diabetes is 

231 



232 CLINICAL PATHOLOGY 

greatly favored by the caries of the teeth and by the organic 
acids, both of which are frequently present in the mouths of 
these patients. The oidium of thrush produces acids, and 
these undoubtedly irritate the mucous membrane directly, and 
favor secondary infections. Acids and alkalies introduced into 
the mouth may destroy its coverings and so cause inflamma- 
tions. The stomatitis of mercurial poisoning is apparently due 
to the action of the mercurial compounds which are excreted 
in the saliva. The stomatitis of scurvy seems to be of a dif- 
ferent character from that caused by other infectious diseases, 
for it develops early in the disease and is particularly severe. 
The scorbutic gingivitis appears to be a specific effect of the 
disease, though its true cause is as little understood as is the 
cause of the other scorbutic manifestations. 

Stomatitis endangers the health of the patient, first, by 
diminishing the ingestion of food, which diminution results 
partly from the tenderness of the mucous membrane, and partly 
from the loss of appetite caused by the disagreeable taste in 
the mouth. In the second place, the number of bacteria in the 
mouth are enormously increased, and vast numbers are swal- 
lowed. The ability of the stomach to disinfect this material is 
limited, its disinfecting power being often most reduced in the 
very diseases with which the stomatitis is associated. The 
passage of large numbers of bacteria from the stomach into the 
intestines may there give rise to abnormal fermentative and 
putrefactive processes, and may even favor a general infection. 

Diminished Secretion of Saliva. — The quantity of saliva is 
diminished in certain infectious diseases, such as pneumonia 
and typhoid fever ; in certain poisonings, as by atropine ; in all 
diseases which are accompanied by great losses of water, such 
as cholera, diabetes, and interstitial nephritis; and, finally, in 
those paralyses of the facial nerve that involve the chorda 
tympani. A diminution of the saliva is always accompanied 
by a reduction in the activity of the buccal mucous glands. 



THE DIGESTION 233 

The resulting dryness of the mouth not only interferes with 
the cleansing of the mouth, but also with the acts of chewing, 
swallowing, and speaking. 

To what degree a lack of ptyalin is injurious has not been 
definitely settled. It was formerly considered that this fer- 
ment played an insignificant part in the process of digestion, 
but we now know that large quantities of starch are converted 
into dextrin in the mouth and in the stomach by the action of 
this ferment. 1 The conversion continues in the stomach even 
after a considerable grade of acidity is present. 

Ptyalism. — An increase in the secretion of saliva, so-called 
ptyalism, may result from an irritation of the chorda tympani 
nerve as it passes through the middle ear. Impressionable 
persons frequently have a marked flow of saliva when they 
think about food or even when they imagine that they have 
taken calomel. Ptyalism also accompanies all irritative condi- 
tions of the mucous membrane of the mouth, such as may 
result, for example, from stomatitis. The ptyalism of mer- 
curial poisoning is due in all probability to a central or periph- 
eral stimulation of the nervous connections of the salivary 
glands. 2 It is possible also that the parenchyma cells are di- 
rectly affected by the poison. Mercurial stomatitis usually 
follows the ptyalism, and is due to some irritating mercurial 
compound present in the saliva. This stomatitis will, in turn, 
increase the salivation, thus establishing a vicious circle. 

There is a remarkable increase in the amount of saliva in 
certain chronic diseases of the medulla oblongata, particularly 
in bulbar paralysis. 3 This has been compared by some authors 
to the paralytic secretion which appears in animals after all 
the salivary nerves have been cut. The latter begins about 

'J. Miiller, Kongr. f. in. Med., 1901, p. 321. 
2 v. Mcring, Arch. f. exp. Path., vol. xiii. p. 86. 

•Kayser, Arch. f. klin. Med., vol. xix. p. 145; Kussmaul, Volkmann's 
Vortriige, No. 54. 



234 CLINICAL PATHOLOGY 

twenty-four hours after the operation, lasts about one week, 
and gradually ceases on account of the degeneration of the 
secreting cells. The two conditions differ, however, in the 
length of time over which the salivation lasts and in the amount 
of saliva secreted, the quantity being much greater in the case 
of bulbar paralysis. It seems to me very probable that the 
ptyalism of bulbar paralysis is not a paralytic secretion, but 
that it is due to an irritation of the cells of the medulla, which 
occurs as they degenerate. It is, therefore, comparable to the 
fibrillary muscular twitchings so often seen when the large 
motor cells of the cord are undergoing degeneration. Certain 
it is that the saliva is really increased in these cases of bulbar 
paralysis, and that the condition is not merely a loss of normal 
saliva occasioned by a paralysis of the muscles of the mouth. 
Indeed, the salivation is frequently present even before the 
muscles have become markedly weakened. 

An increased flow of saliva may be caused, finally, by 
reflexes from other parts of the body, as from an ulcer of 
the stomach, from the uterus during pregnancy, from the 
trigeminal nerve in cases of trifacial neuralgia, etc. 

In all these conditions the saliva presents the characteristics 
of that obtained by stimulation of the chorda tympani; i.e., it 
is increased in amount, but poor in solids. 

An increased secretion of saliva is especially unpleasant 
when it drips from the mouth, as happens in cases of bulbar 
paralysis. Yet even when it is swallowed it may be disadvan- 
tageous, for the large quantity of alkaline, mucous fluid, rich 
in bacteria, is injurious to gastric digestion. 

Composition and Reaction of the Saliva. — The saliva may 
contain abnormal constituents, such, for example, as the com- 
pounds of iodine, when the latter have been administered. 
Whether other substances pass into the saliva or not depends 
largely upon the amount present in the plasma. Urea is thus 
excreted only in those pathological conditions which increase 



THE DIGESTION 235 

its concentration in the blood, as in severe nephritis. Other 
constituents of the blood, such as sugar, rarely pass into the 
salivary secretion. It is unnecessary to enumerate the various 
substances which sometimes appear in the saliva, for the sub- 
ject has but little pathological significance. 

The reaction of the saliva varies in the healthy individual 
during the process of digestion. In the fasting condition it 
is usually weakly acid, but after taking food it becomes alka- 
line. On the other hand, in diabetes, in fever, and in dyspeptic 
individuals, it is not infrequently constantly acid; in some 
instances owing to the presence of the products of bacterial 
decomposition. The pure parotid saliva is said to be acid 
in severe diabetes, but the cause of the acidity is not known, 
and some observers have even found it to be alkaline in 
severe forms of the disease. 4 

Swallowing. — The passage of food from the mouth into 
the oesophagus is accompanied by special dangers, for it must 
cross the respiratory tract in the pharynx. The trachea must 
be closed off below by the epiglottis, and the nasal passage 
above by the soft palate and the superior constrictors of the 
pharynx. This intricate mechanism is controlled by reflexes 
through the trigeminal and vagus nerves. The centripetal 
impulses arise from the mucous membrane of the throat, and 
the centre which presides over swallowing is situated in the 
medulla. 

Disturbances of the act of swallowing may be caused by a 
diminished irritability either of the centre or of the sensory 
nerves. This is seen in certain intoxications, notably morphine, 
chloroform, chloral, diabetic coma, and ursemic coma, as well 
as in some diseases of the nerves. Disturbance of swallowing 
may also arise from a paralysis of the necessary muscles, 
caused either by a disease of the motor nuclei in the medulla, 
as in bulbar paralysis or medullary tumors, or by a neuritis 
4 Ganigcc, Phys. Chcm. d. Verdauung, Leipzig, 1897, p. 50. 



236 CLINICAL PATHOLOGY 

of the nerves themselves, such as is seen so frequently after 
diphtheria. Furthermore, difficulty in swallowing may arise 
not from a paralysis, but from a spasm of the necessary 
muscles, as occurs in hydrophobia, tetanus, and hysteria. 
Finally, defects in the palate, usually caused by syphilitic 
ulcerations, interfere with the act of swallowing. 

In these conditions, the food may pass either into the 
nose or into the trachea. The latter is the more serious, for 
if the food, with its many bacteria, enters the lungs, pneu- 
monia and not infrequently gangrene result. The entrance 
of food into the nasal cavity is less dangerous. Coughing 
and sneezing are the usual results. Yet these may cause the 
patient such great discomfort that he refrains from eating, 
and it is even possible that a large portion of his nourishment 
should be lost through the nose. 

When swallowing is painful, the patient may take insuffi- 
cient nourishment, just as is the case when chewing is painful. 

(Esophageal Stenosis. — Diseases of the oesophagus usually 
produce symptoms by obstructing the passage of food. This 
obstruction may be due, in the first place, to a muscular spasm, 
as in hydrophobia and hysteria. Such an oesophageal spasm 
is rarely very serious, because in the case of hysteria it is 
usually finally overcome, and in hydrophobia there are other 
more immediate dangers. 

Of greater importance are permanent obstructions, such 
as may be caused by the contraction of scar tissue, by tumors, 
or by pressure from without. The milder stenoses only inter- 
fere with the swallowing of the coarser foods ; the more severe 
ones may stop even fluids. Normally we do not feel our food 
after it has once passed the pharynx, but the patient with an 
obstruction in his oesophagus often complains that he can feel 
the food stop in a definite place. Above the point of obstruc- 
tion the oesophagus usually becomes dilated, owing to the 
stasis of material. The muscular tissue surrounding the dila- 



THE DIGESTION 237 

tation undergoes hypertrophy, and it is then probably better 
able to force food past the stenosis. Some of that which does 
not pass stagnates in situ, undergoing decomposition. The 
remainder is immediately returned into the mouth. This re- 
gurgitation of food is quite different from vomiting, and the 
patient himself usually appreciates the difference; for the food 
swallowed appears to return of itself, he experiences no 
nausea, and his abdominal muscles are not brought into action. 
Apparently the obstruction to the passage of food increases the 
contractions of the muscular tissues of the oesophagus. Many 
believe that the increased pressure on the food simply forces 
it upward, and that there is no true antiperistalsis in these 
cases. Personally, however, I see no reason to exclude the 
possibility that antiperistaltic movements do play a part in the 
regurgitation of food. 5 

Pressure Diverticula. — The so-called pressure diverticula 
usually spring from the upper and posterior part of the oesopha- 
gus. They seem to originate from a primary weakness of the 
oesophageal wall, produced by such causes as foreign bodies, 
traumatisms, or possibly congenital defects in the muscle. The 
wall of the diverticulum is composed of the mucous membrane, 
the submucosa, and a thin layer of muscle. As the sac becomes 
larger, a part of the food passes into it instead of going down 
the oesophagus. This food is in part immediately regurgitated, 
but enough may remain in the diverticulum to press upon the 
oesophagus and so to occlude it. It is only after the sac has 
been emptied of its contents that a free passage is again 
opened into the stomach. The symptoms caused by such a 
diverticulum vary greatly, depending, for the most part, upon 
the ease with which the sac is filled and emptied. The food 
which stagnates in the sac may decompose and cause ulcerations 
of the mucous membrane, and these in turn may give rise to 

6 Starch, Arch. f. klin. Med., vol. lxvii. pp. I, 201, 383; Brosch, ibid., 
vol. lxvii. p. 45; Riebold, ibid., vol. lxxx. p. 527. 



238 CLINICAL PATHOLOGY 

very severe pains. A pressure diverticulum is therefore a 
considerable menace to the health of the patient, and it is 
fortunate that the condition is a rare one. 

Primary Dilatation of the (Esophagus. — Difficulties in 
swallowing may be caused by a diffuse or localized oesophageal 
dilatation, unaccompanied by any demonstrable anatomical 
obstruction. 6 It is very probable that in many of these cases 
the dilatation is due to a functional stenosis, originating in a 
spasm of the muscle at the lower end of the oesophagus. Such 
spasms may be primary, or they may be caused by ulcerations 
of the mucous membrane. In some instances the dilatation has 
a congenital origin. The symptoms of such dilatations are very 
similar to those of ordinary stenoses, — viz., obstruction to the 
passage of food, stasis in the dilated sac, and regurgitation. 
When there is a partial anatomical stenosis, or a functional 
stenosis from spasm of the cardia, the symptoms may persist 
for many years with intermissions of perfect health. The symp- 
toms sometimes resemble those of rumination, especially if the 
dilatation affects that portion of the oesophagus which lies 
between the diaphragm and the cardiac orifice of the stomach. 

In another class of cases, the course of the disease is ex- 
ceedingly rapid, and autopsy discloses an oesophagus widely 
dilated, filled with food, and yet without any demonstrable 
stenosis. A condition similar to this may be produced ex- 
perimentally by cutting both vagi in the neck of a dog. 7 This 
operation causes a paralysis of the oesophageal musculature, 
so that, even though the cardia apparently remains open, food 
does not pass into the stomach, but accumulates in the oesopha- 
gus and causes death. The cases of acute oesophageal dilata- 
tion in man, above referred to, are probably due to just such 
a primary paralysis of the muscle, depending possibly upon a 
lesion of the vagi nerves. 

8 Zusch, Arch. f. klin. Med., vol. Ixxiii. p. 208. 
"Krehl, Du Bois' Arch., 1892, p. 278. 



THE DIGESTION 239 

Painful sensations rarely originate in the oesophagus, first, 
because painful affections, such as ulcer, are rare in this portion 
of the digestive tract, and secondly, because this is a com- 
paratively insensitive organ. Yet, as we have already men- 
tioned, diverticula may occasion great pain. 

Rupture of the oesophagus is very rare. It is usually a 
complication of some definite lesion of the wall, such as 
carcinoma or erosion from acids or alkalies. It may, however, 
occur in apparently healthy individuals, though the cause of 
the rupture in such cases is unknown. 

The Stomach. — The stomach acts as a reservoir for the 
large quantities of food which are ingested at each meal. Some 
of this food is absorbed in the stomach, but most of it, including 
practically all the water, is gradually passed on into the duo- 
denum, after having been acted upon by the gastric juice. 
Strangely enough, the opinion has become current that the 
stomach is a superfluous organ. It is, indeed, true that 
animals as well as men have continued to live after the stom- 
ach has been practically entirely extirpated, and that life may 
be maintained by artificially introducing food into the intes- 
tines below the stomach. 8 Indeed, a dog without a stomach 
may live on quite a varied diet, even though it include decom- 
posing meat. 9 Interesting and important as these facts are, 
nevertheless it remains true that the less a man has cause to 
consider his digestion, the better is his health; and the 
stomach stands as a most important preparatory organ, which 
receives the varying kinds and quantities of food, and shields 
the more delicate intestines from the harm which these foods 
might produce if directly introduced. 

It is possible to obtain pure gastric juice from animals, 10 

8 Kaiser, Czerny's Beitrage, 1878 ; Ogata, Du Bois' Arch., 1883, p. 39 ; 
Deganello, Arch. ital. de Biol., vol. xxxiii. p. 118. 

' Carvallo and Pachon, Arch, de physiol., 1894, p. 106. 
10 Pawlow, The Work of the Digestive Glands. 



240 CLINICAL PATHOLOGY 

but from man we are only able to obtain mixtures containing 
both gastric juice and food. For this reason it is impossible to 
make very accurate studies of the gastric secretion of man. 

At the height of digestion the hydrochloric acid is present 
in the stomach in various combinations. In the first place, 
some has united with the inorganic bases or basic salts of 
the food, or has even decomposed salts of the weaker acids. 
Secondly, a portion of the hydrochloric acid combines with 
certain basic organic compounds. 11 Of these, the most im- 
portant practically are the combinations between the hydro- 
chloric acid and the various proteids of the gastric contents. 
These combinations possess an acid reaction and some anti- 
septic properties, and are able to assist the pepsin in hydro- 
lyzing proteids, though their action here is less efficient than 
is that of free hydrochloric acid. Finally, a certain amount 
of free, uncombined hydrochloric acid is usually present in 
the gastric contents. Yet this may be absent, even at the 
height of digestion, in some individuals, and it is questionable 
whether such an absence is always pathological or not, for 
some of these individuals appear to be in perfect health. 

The total amount of acid secreted depends mainly upon 
the quantity and quality of the food taken. The secretion 
apparently continues until the free and combined hydrochloric 
acid in the gastric contents reaches a certain percentage, 
amounting normally to about 0.2 to 0.3 per cent. Precisely to 
what degree the secretion of acid depends upon the quantity 
of nourishment, and to what degree it is subject to individual 
variations, has not been completely worked out. Organic acids 
may be introduced in the food, but they are not formed in the 
healthy stomach, 12 and lactic acid, for example, is never a 
product of normal gastric digestion. 

11 F. A. Hoffman, Ztrbl. f. in. Med., vol. xi. p. 521. 

12 Martius and Leuttke, Die Magensaure des Menschen, Stuttgart, 
1892; Boas, Ztft. f. klin. Med., vol. xxv. p. 285. 



THE DIGESTION 241 

The Disturbances of Gastric Secretion. — The mucous 
membrane of the stomach usually continues to manufacture the 
zymogens of pepsin and rennin, even though the secretion 
of hydrochloric acid has partly or wholly ceased. Only in the 
most advanced changes of the mucosa are these ferments much 
diminished or altogether absent. Such a lack of ferments may 
be seen in advanced atrophic gastritis, in carcinoma of the 
stomach, and in certain neuroses (so-called achylia gastrica). 
Thus no simple relation exists between the amounts of acid 
and of ferments present in the gastric juice. 13 The former is 
usually the first to disappear under pathological conditions, 
and the ferments may or may not follow it. The secretion of 
rennin and of the fat-splitting ferment 14 seems to vary simul- 
taneously with the secretion of pepsin. In studying cases of 
impaired gastric secretion, therefore, it is necessary to consider 
both the acids and the ferments. 

Xo symptoms are necessarily produced by a mere absence 
of gastric juice so long as the motility of the stomach remains 
good, and it is a remarkable fact that this motility is often 
increased in cases of achylia. We are still very poorly ac- 
quainted with the anatomical changes in the mucous membrane 
which lead to a cessation of gastric secretion, and especially 
are we ignorant as to the role which nervous influences may 
play in producing this condition. 

What furnishes the normal stimulus to gastric secretion? 
In dogs, at least, the appetite plays a leading role, 15 but this 
appears to be less true for man. It would seem that the 
human mucous membrane is directly stimulated to secretion 
by the presence of proteid food in the stomach, and that this, 
together with certain reflexes, exercises a greater influence upon 

13 Roth, Ztft. f. klin. Med., vol. xxxix. p. i; Gintl, Arch. f. Verdau- 
ungskr., vol. iv. ; Troller, ibid., vol. v. p. 150. 

"Volhardt, Ztft. f. klin. Med., vol. xlii. p. 414. 

"Pa\vlow, The Work of the Digestive Glands; Lang, Arch. f. klin. 
Med., vol. lxxviii. p. 302. 

16 



242 CLINICAL PATHOLOGY 

gastric secretion than does the appetite. 16 The saliva and the 
chewing of food may also be of some importance. 17 

(Recent observations 1S upon a patient with a gastric fistula 
have furnished us with some important data concerning human 
gastric juice and the factors which influence its secretion. The 
stomach of this patient was found to be empty so long as he 
fasted, providing that he took care not to swallow his saliva. 
Chewing gum did not give rise to a gastric secretion, whereas 
the chewing of food or the mere rinsing out of the mouth 
with brandy was sufficient to start the flow of gastric juice, 
evidently because these articles stimulated the appetite. Even 
the mere passage of food before the eyes of the hungry patient 
was enough in one instance to excite a flow from the stomach. 
In view of these direct observations, which are completely 
analogous to those made by Pawlow on dogs, it cannot be 
doubted that the appetite plays a most important part in regu- 
lating the gastric secretions of man. 

The secretion obtained in these experiments began about 
three minutes after the introduction of food into the mouth, 
and reached its maximum in from ten to fifteen minutes, finally 
ceasing after about an hour. The hydrochloric acid was pres- 
ent in greatest concentration during the first half-hour, and 
reached as high a percentage as 0.35 per cent. — Ed.) 

Hypersecretion of Gastric Juice. — The stomach of a 
healthy fasting man is either empty or it contains a small 
amount of fluid, which may or may not show free acid. Some 
authors believe that the fasting stomach is always empty, 19 
while others hold that it usually contains active gastric juice 
which sometimes amounts to fifty or one hundred cubic centi- 
metres. In our experience it has been found empty in some 

"Schiile, Arch. f. klin. Med., vol. lxxi. p. in. 

17 Schiile, Arch. f. Verdauungskr., vol. v. p. 165. 

"Umber, Berl. klin. Wochens., 1905, p. 56. 

19 Reigel, Nothnagel System ; Ewald, Klinik d. Verdauungskr. 



THE DIGESTION 243 

cases, while in others it has contained a small quantity of 
secretion, possibly caused by material (saliva) swallowed. 

Pathologically, the stomach may contain large amounts of 
fluid, even when the patient is fasting. The percentage of 
hydrochloric acid in this abnormal secretion may be normal or 
it may be excessive, up to 0.4 or 0.5 per cent. After a meal 
the secretion and the percentage of acid may be still further 
increased; yet this does not always occur, and it is possible 
that at the height of digestion the gastric contents of these 
patients should appear to be perfectly normal. 

Such a continuous hypersecretion has been met with in 
chronic dyspepsia. 20 It may also occur as a transitory or 
periodic condition in certain nervous diseases, — such as tabes, 
neurasthenia, and hysteria. 21 The cause of the hypersecretion 
appears to be an increased irritability either of the mucous 
membrane of the stomach or of its secretory nerves. In many 
cases, even after a long period of hypersecretion, no anatomi- 
cal changes are demonstrable in the gastric mucous mem- 
brane, 22 which would seem to indicate that, in these cases at 
least, the condition was of nervous origin. It is possible that 
a hypersecretion may sometimes be caused by a stimulation 
of the secretory centres in the brain, and, when this is so, the 
condition would be comparable to the salivation that is so often 
present in progressive bulbar paralysis. 

Chronic hypersecretion is frequently met with in association 
with dilatation of the stomach. A number of clinicians, among 
them Riegel, regard the dilatation as secondary to the hyper- 
secretion. According to others, 23 however, the dilatation is 

"Reichmann, Berl. klin. Wochens., 1882, No. 40, 1884, No. 48, 1887, 
No. 12; Riegel, Deut. med. Wochens., 1904, Nos. 20 and 21. 

* Ewald, Klinik d. Verdauungskr. ; Rossbach, Arch. f. klin. Med., 
vol. xxxv. p. 383. 

"Oestreich, Verein f. in. Med., in Berlin. Deut. med. Wochens., 1895, 
No. 21 ; Fcrrand, Centralbl. f. Path., vol. vii. p. 769. 

23 Schreiber, Arch. f. Verdauungskr., vol. ii. p. 423. 



244 CLINICAL PATHOLOGY 

primary and the hypersecretion results from an over-stimula- 
tion of the mucous membrane by the stagnated food. 

In all these conditions the secretion of gastric juice is con- 
tinuous even during fasting. In another group of cases, the 
stomach is found to be empty between meals, but when food is 
introduced it reacts with an over-production of normal gastric 
juice or with the production of an abnormally acid secretion. 
In this subject we are greatly handicapped by our relative 
ignorance as to the manner in which the stomach normally 
responds to the introduction of various kinds and quantities of 
food. It is usually assumed that the large amount of acid 
present in these cases is hydrochloric acid, and in most in- 
stances this is certainly true, for an acidity of 0.5 per cent, in 
the absence of organic acids allows of hardly any other inter- 
pretation. Still a greater precision in this matter is desirable. 

Round Ulcer of the Stomach. — Round ulcer of the 
stomach is usually accompanied by hyperacidity. The relation 
between the two is of interest, because some authors have held 
that the excess of acid produces the ulcer. That some relation 
does exist between the two is shown by the fact that round 
ulcers only occur in localities exposed to acid secretions 
(stomach and duodenum). Yet, ordinarily, abrasions of the 
gastric mucous membrane heal with great rapidity. 24 The 
wall of the stomach contracts opposite the injured point, which 
is thus somewhat protected from the action of the gastric juice, 
and the epithelium then rapidly extends over the defect. The 
round ulcer of the stomach as seen in man differs from such 
an abrasion mainly in its chronicity. 

A double etiological relation seems to exist between hyper- 
acidity and ulcer of the stomach. On the one hand, the irrita- 
tion of the nerves at the base of the ulcer seems to increase 
the secretion of gastric juice. On the other, a hyperacidity 

"Matthes, Ziegler's Beitrage, vol. xiii. p. 309; A. Schmidt, Kongr. 
f. in. Med., 1902, p. 270. 



THE DIGESTION 245 

would interfere with the healing of any defect in the mucous 
membrane, and an anatomical lesion would then be more liable 
to lead to a chronic ulceration. A number of facts indicate 
that the hyperacidity alone is not the cause of the ulcer. 
Thus ulcers may occur without hyperacidity, 25 though it must 
be admitted that in these cases the latter may have been present 
at some earlier stage of the process. Conversely, individuals 
may show a most marked hyperacidity for years without de- 
veloping an ulcer. Other factors must therefore be present, 
and at best the hyperacidity is only a contributing cause. Of 
other factors which have been described, we may name general 
anaemia, local anaemia of the gastric mucosa, produced by 
thrombosis of blood-vessels, etc., and, finally, local trauma- 
tisms, whether mechanical, thermic, or chemical. The acid 
does not apparently attack the healthy mucous membrane, yet 
it may possibly do so if the latter is weakened by some of these 
accessory causes. When the ulcer has once formed, the acid 
seems to prevent the formation of healthy granulation tissue, 
the base of the ulcer becomes thickened, and healing is rendered 
difficult. 20 

(Infectious thromboses situated in the gastric mucous mem- 
brane seem to be capable of leading to acute ulcers, the so-called 
hemorrhage erosions. This is apparently the cause of the 
severe gastric hemorrhage which sometimes follows an abdomi- 
nal operation. Chronic round ulcers, however, rarely follow 
these erosions. 

Experimentally it is extremely difficult to produce a gastric 
ulcer that presents the anatomical features characteristic of the 
chronic round ulcer of man. As has been previously staled. 
a mere abrasion of the epithelium, from whatever cause, gen- 
erally heals quite rapidly. The most successful experiments 

"Gerhardt, Deut med. Wochens., 1888, No. 18; Lenhartz, ibid., 1890, 
No. 60; Du Mesnil, Munch, mcd. Wochens., 1894, No. 50. 

"Korczynski and Jaworski, Arch. f. klin. Mcd., vol. xlvii. p. 578. 



246 CLINICAL PATHOLOGY 

are those in which the pneumogastric nerves of rabbits have 
been divided. 27 Following this operation, round ulcers of 
chronic course and of typical anatomical structure have de- 
veloped in some instances. It is not known in what way sec- 
tion of the vagi affects the gastric mucosa, whether it is by 
interfering with protective reflexes or by shutting off trophic 
influences. No observations, directed to the possibility that 
the round ulcer of man might be caused by lesions of the vagus 
nerve, have yet been made. — Ed.) 

Effects of Hypersecretion and Hyperacidity. — In discuss- 
ing the effects of an excessive secretion of hydrochloric acid, 
it is possible to consider both hyperacidity and hypersecretion 
together. Disturbances are produced by the excess of acid; 
and these occur during digestion in cases of pure hyperacidity, 
or during fasting in cases of continuous hypersecretion. As 
Riegel has said, the effects result in both cases rather from the 
profuse secretion than from the high acidity of the juice 
secreted. In the presence of an excess of acid, the digestion 
of starch in the stomach ceases altogether. The proteids are 
digested, but it is not known whether this digestion follows a 
normal course or not. The patient frequently suffers from 
severe pains and from vomiting, for both of which the hyper- 
acidity is usually directly responsible, for they are usually re- 
lieved by the administration of substances which will combine 
with acids, such as alkalies and proteids. 

The effect of an increased secretion upon the gastric 
motility will be discussed in another place, though we may 
mention here that not infrequently a hypersecretion is followed 
by dilatation of the stomach ( Riegel ) . What effect the hyper- 
acid gastric contents exert upon the intestines and upon the 
intestinal digestion is not definitely known. Possibly the poor 
nutrition of many patients with hyperacidity is due to the 

27 van Yzeren, Ztft. f. klin. Med., vol. xl. p. 181 ; W. Ophuls, Personal 
Communication. 



THE DIGESTION 247 

difficulty in neutralizing the hyperacid material which reaches 
the intestines and to a consequent insufficient absorption of 
nourishment. 

The symptoms of gastric ulcer are, in part, those of hyper- 
acidity; yet the pains are usually more intense, probably be- 
cause the base of the ulcer is especially sensitive. Then, too, 
a series of complications may follow in the train of the ulcer. 
Arteries may be eroded and hemorrhage ensue; the gastric 
wall may be perforated, with the resultant adhesions, abscesses, 
or peritonitis. The number of such complications is unfor- 
tunately a large one. 

Subacidity and Anacidity. — It is necessary to be very 
careful in our judgment of those cases in which the amount of 
free hydrochloric acid in the gastric contents is found to be 
diminished, for this may be brought about in two ways, — 
either by an actual diminution in the secretion, or by a neu- 
tralization in some abnormal manner of the acid secreted. To 
estimate the total amount of hydrochloric acid secreted it is 
necessary to know the total quantity of chlorides in the gastric 
contents, and to subtract from this the chlorides of the food. 

Free hydrochloric acid is absent in many acute gastric dis- 
turbances, functional as well as anatomical, notably in those 
associated with the acute infectious diseases. Anacidity is seen 
more frequently, however, in chronic diseases of the stomach, 
as in atrophy or amyloid degeneration of the mucous mem- 
brane, and especially in carcinoma. Even diseases outside of 
the stomach may inhibit the gastric secretion ; and carcinomata 
situated in the abdominal cavity, pernicious ansemia, advanced 
tuberculosis, and cachexia may all be associated with an absence 
of free hydrochloric acid in the gastric contents. A mere 
reduction in the amount of the free hydrochloric acid occurs 
in a great variety of conditions, especially in the chronic dys- 
pepsias. In all these cases more data arc needed as to the 
total amount of acid which has been secreted. 



248 CLINICAL PATHOLOGY 

These relations have been carefully studied in gastric car- 
cinoma. The diminution or absence of free hydrochloric acid 
in the stomach contents of such patients may be due, as we 
have said, either to a lessened secretion of acid or to an in- 
creased production of compounds which will bind the acid. 
Both conditions appear to be present in cases of gastric carci- 
noma. The diseased condition of the gastric mucous mem- 
brane which is demonstrable in many cases of carcinoma might 
readily lead to a diminished secretion of acid. 28 On the other 
hand, the carcinoma apparently produces substances which 
tend to neutralize the acid secreted, and in many cases con- 
siderable hydrochloric acid must be added to the gastric con- 
tents before a reaction for free acid will appear. The sub- 
stances which cause the acid to disappear are apparently of 
the nature of enzymes, for they are destroyed by heat. 29 That 
hydrochloric acid is secreted in carcinoma is shown by the 
fact that the quantity of combined chlorides may equal or 
exceed the normal. 30 If the carcinoma develops on an old 
ulcer of the stomach, free hydrochloric acid is usually present 
in the gastric contents, and often in excessive quantities. 31 

When the hydrochloric acid in the gastric contents is re- 
duced, the ptyalin is able to act for a long time upon the food, 
unless its action should be interfered with by the presence of 
organic acids. Digestion of the proteids is usually diminished 
or absent, according to the reduction in the amount of hydro- 
chloric acid. (A carcinoma of the stomach, however, appar- 
ently produces ferments which are able to decompose proteids 
even more rapidly than does the normal gastric juice. 32 — Ed.) 

28 Rosenheim, Berl. klin. Wochens., 1888, Nos. 51 and 52; Hammer- 
schlag, Arch. f. Verdauungskr., vol. ii. pp. 1, 198; Reissner, Ztft. f. klin. 
Med., vol. xliv. p. 87. 

20 Emerson, Arch. f. klin. Med., vol. lxxii. p. 415. 

30 Cahn and Mering, Arch. f. klin. Med., vol. xxxix. p. 233 ; Reissner, 
Ztft. f. klin. Med., vol. xliv. p. 87. 

31 See Hirschfeld, Kongr. f. in. Med., 1902, p. 279. 

32 See Emerson, loc. cit. 



THE DIGESTION 249 

A diminished proteid digestion in the stomach does not neces- 
sarily mean a loss of food material to the body, for with a 
proper dietary the intestinal digestion can compensate for the 
inefficiency of the stomach, and the nitrogenous material in the 
body may not only be maintained at the old level, but in some 
cases the store may be actually increased. 33 

Bacterial Action in the Stomach. — An abundant multipli- 
cation of bacteria within the stomach is prevented mainly by 
the normal evacuation of its contents. Even though hydro- 
chloric acid is absent, no bacterial decomposition ordinarily 
takes place so long as the motility of the stomach remains 
good and its contents are regularly passed on into the in- 
testines before the bacteria have time to multiply. The main 
factor favoring bacterial decomposition is stagnation of ma- 
terial, and, when this is present, the grade of acidity present 
plays a most important part in determining the variety of 
micro-organisms which shall multiply, and consequently the 
character of the decompositions which these shall produce. 

The normal gastric juice possesses decided antiseptic prop- 
erties, owing principally to its acidity. Whether the pepsin 
is of great importance or not in this respect is still a matter of 
dispute. Cells are usually digestible only when they are dead ; 
yet it has been claimed that the pepsin plays an important part 
in limiting bacterial growth, more especially the growth of 
those bacteria which give rise to the lactic acid fermentation. 34 
An acidity of 0.2 per cent, in a test-tube will after a time 
destroy many bacteria, such, for example, as the typhoid bacil- 
lus and the cholera vibrio, whereas other bacteria and espe- 
cially spores are not greatly injured by this amount of acid. 
Yet the conditions in the test-tube are not the same as those in 
the stomach. Many parts of the food do not come into inti- 
mate contact with the gastric juice at all, cither because they 

M v. Noorden, Ztft. f. klin. Med., vol. xvii. pp. i.37, 45^, 5M- 
** Hammerschlag, Arch. f. Verdauungskr., vol. ii. p. I. 



250 CLINICAL PATHOLOGY 

are quickly passed on into the intestines or because they lie in 
the centres of large particles which are not broken up in the 
stomach. Furthermore, a large part of the hydrochloric acid 
secreted is immediately bound by the proteids, etc., and these 
combinations are known to be less antiseptic than is free hy- 
drochloric acid, though even they may kill cholera bacilli. 35 
It is evident, therefore, that the bactericidal powers of the 
gastric secretion are limited, and that numbers of micro- 
organisms are being constantly passed on into the intestines. 

If free and abundant hydrochloric acid be present in stag- 
nated gastric contents, the ordinary putrefactive decomposi- 
tions of proteid material rarely take place. The fermentation 
of carbohydrates, however, does occur : sugar is transformed 
into alcohol and carbon dioxide, alcohol into acetic acid, dex- 
trose into lactic acid, butyric acid, carbon dioxide, and hydro- 
gen, etc. The gases which ordinarily result from these fermen- 
tations are carbon dioxide, hydrogen, and traces of methane. 
These, together with swallowed air, usually make up the bulk 
of the gases present in the stomach during gastric fermenta- 
tions. 36 Each of these fermentations may be carried on by a 
number of micro-organisms that will resist an acid reaction of 
not too high a grade, 37 but yeasts and sarcinse are those most 
commonly found. 

If the stagnation is accompanied by a diminution or absence 
of hydrochloric acid, then opportunity is given for the multi- 
plication of a greater variety of micro-organisms. These may 
even cause putrefaction of proteid material. More frequently, 
however, they give rise to fermentative processes similar to 
those just described. Yet there is a special tendency to the 

35 Minkowski, Mitth. aus d. med. Klinik z. Konigsberg, Leipzig, 1888; 
Kabrehl, Arch. f. Hyg, vol. x. p. 382. 

30 Hoppe-Seyler, Kongr. f. in Med., 1892, p. 392; ibid., Arch. f. klin. 
Med., vol. 1. p. 82. 

37 Strauss and Bialoour, Ztft. f. klin. Med., vol. xxviii. p. 567. 



THE DIGESTION 251 

production of lactic, butyric, and other volatile organic acids. 38 
The lactic acid fermentation is particularly characteristic of 
gastric stagnation in the absence of hydrochloric acid; and 
if this be present in sufficiently large quantities it tends to 
inhibit the growth of many bacteria which would otherwise 
give rise to putrefactive processes. A special lactic acid 
bacillus (Oppler-Boas bacillus) is then frequently present in 
enormous numbers in the gastric contents. 

From a consideration of these facts it will be seen that no 
one kind of bacterial decomposition is pathognomonic of any 
particular clinical condition. The decomposition depends 
rather upon the varieties of micro-organisms which have been 
introduced into the stomach, upon the opportunity which they 
have had to multiply, and upon the kind of food which is sub- 
jected to their activities. The relation between carcinoma of 
the stomach and the lactic acid fermentation must be judged 
from just such a general stand-point. The two frequently 
occur together ; but this depends upon the fact that stagnation, 
absence of free hydrochloric acid, and diminution in the fer- 
ments are frequently present in carcinoma of the stomach, 
and that these are the very conditions which favor the develop- 
ment of the lactic acid fermentation. If, as rarely happens, 
the combination of a gastric stagnation and an absence of free 
hydrochloric acid is caused by some condition other than car- 
cinoma, then the lactic acid fermentation might equally well 
occur there. Very remarkable decompositions have been ob- 
served in some stomachs, such, for example, as the production 
of sulphuretted hydrogen when free hydrochloric acid was 
absent. 39 

The acidity of the gastric contents exerts no small influ- 
ence upon the chemical processes in the intestines, and we may 
say here that, in general, as the acidity in the stomach dimin- 

88 Rosenheim and Richter, Ztft. f. klin. Med., vol. xxviii. p. 505. 
80 Boas, Deut. med. Wochcnschr., 1892, No. 49. 



252 CLINICAL PATHOLOGY 

ishes, the putrefaction in the intestines tends to increase. This 
subject will be more fully considered below. 

It sometimes happens that fermentation occurs in the gas- 
tric contents, even though there is no diminution either in the 
secretion of acid or in the motility of the stomach. In such 
cases it is possible that the fermentation is due to the introduc- 
tion of excessive amounts of fermentable material, together 
with the agents which cause the fermentation. 40 This fermen- 
tation would in turn affect the gastric motility, and that would 
favor further fermentation. 

Abnormal fermentative processes do harm to the stomach 
in various ways. The products of fermentation may irritate 
and injure the gastric mucosa, producing loss of appetite, pains, 
vomiting, and possibly spasmodic stricture of the pylorus with 
diminished gastric motility. Gases may be produced in large 
quantities, causing abdominal distention and belching. The 
abnormal secretion of fluid by the stomach, together with the 
distention by gases, would favor the development of gastric 
dilatation. At times toxic substances are produced in gastric 
fermentations, and these may give rise to a varied category of 
general symptoms (see p. 259). 

We know very little about the function of the mucus 
secreted by the stomach, which is unfortunate, because it is 
quite probable that this may exert some protective influence 
in certain pathological conditions. 

THE DISTURBANCES OF GASTRIC MOTILITY 

The normal movements of the different parts of the stom- 
ach are fairly well known. The fundus acts as a reservoir 
for the food. Its wall shows peristaltic movements, but the 
pressure within it is comparatively low. The antrum pylori- 
cum contracts periodically, several times a minute, although it 
may at times contract irregularly. During a contraction the 

40 Naunyn, Arch. f. klin. Med., vol. xxxi. p. 225. 



THE DIGESTION 253 

pressure exerted upon its contents is considerable, over a half- 
metre of water in man. 41 Since its cavity is shut off from the 
fundus by the sphincter-like action of its proximal portion, its 
contents may be thrown through the relaxed pylorus into the 
intestines. (The relaxation of the pylorus in the normal stom- 
ach seems to depend upon the presence of free hydrochloric 
acid in the stomach contents. When particles of food are 
present in the stomach, the pylorus is closed, but with the 
appearance of free acid it relaxes, and some of the acid con- 
tents are allowed to pass through into the intestines. The 
effect of the acid within the duodenum is to cause, on the one 
hand, a closure of the pylorus behind, and, on the other, to 
stimulate the flow of the alkaline secretions of the pancreas. 
These will in time neutralize the acid in the duodenum, and 
when this is effected the pylorus can again relax and allow 
more of the acid gastric contents to pass through. By this 
mechanism a gradual emptying of the stomach into the intes- 
tines is affected. Since proteids combine with the acid which 
is first secreted, and thus delay the appearance of free acid in 
the gastric contents, they do not leave the stomach so soon 
as do carbohydrates or fats. 42 — Ed.) The antrum pyloricum 
seems to pick the fluid and finely divided portion of the gastric 
contents out of the fundus, and in this manner it regulates still 
further the emptying of the stomach. 43 

The cause of the gastric movements is very uncertain. In 
the first place, like all other unstriated muscles, the stomach 
has periods of rest alternating with periods of activity. Some 
have believed that the acidity exerts a great influence upon the 
gastric movements, yet we know that, under pathological con- 
ditions at least, no definite relation exists between the motility 
of the stomach and the acidity of its contents. On the one 

41 Mortiz, Ztft. f. Biol., vol. xxxii. p. 313. 

"Cannon, Jour, of the Am. Med. Assoc., 1905, p. 15. 

"v. Mcring, Kongr. f. in. Med., [897, p. 433. 



254 CLINICAL PATHOLOGY 

hand, we see diminished motility combined with hyperacidity, 
and, on the other, increased motility with an entire absence 
of free hydrochloric acid. The consistency of the contents cer- 
tainly influences gastric motility. Large solid particles are 
thrust back into the fundus by the antrum, whereas soft masses 
are allowed to pass through into the intestines. Warm ma- 
terial tends to increase the peristalsis and to relax the pyloric 
sphincter. 44 Although careful studies have been made as to 
the length of time that certain foods remain in the stomach, yet 
more work is needed upon abundant mixed diets. 45 

Increased Peristalsis and Increased Gastric Motility. — At 
times, the peristaltic movements of the stomach are increased, 
and its contents are emptied more rapidly than normal. Yet 
this rapid emptying does not necessarily occur; for, when 
a hinderance to the exit of food is present, the powerful con- 
tractions of the muscle may be unable to expel the food even 
within the normal period of time. Frequently the patient is 
rendered extremely uncomfortable by the excessive gastric 
peristalsis, and the movements of the stomach may be 
plainly visible through the abdominal wall. In some cases 
this condition of " peristaltic unrest" is dependent upon a 
primary pyloric stenosis ; in others, it is probably caused by an 
excessive irritability of the nervous connections of the stomach, 
and it is then frequently accompanied by violent peristalsis of 
the intestines. As we have already said, the stomach may 
empty itself with unusual rapidity in achylia gastrica, though 
this rapid emptying is not usually associated with any sensa- 
tions of increased peristalsis. 

Motor Insufficiency and Gastric Dilatation. — Whenever 
the stomach does not empty itself within the normal limits of 
time, we speak of a motor insufficiency. So long as the dis- 
turbance of motility is slight, it may be of but little conse- 

** Schiile, Ztft. f. klin. Med., vol. xxix. p. 80. 
45 Penzoldt, Arch. klin. Med., vol. li. p. 535. 



THE DIGESTION , 255 

quence; but should it become so pronounced that food par- 
ticles remain continuously in the stomach, then fermentations 
are apt to injure the mucous membrane owing to the produc- 
tion of abnormal acids and to distend the muscle by abnormal 
gases, and then a dilatation of the stomach may ensue. This 
dilatation is especially favored in some instances by the secre- 
tion of large quantities of fluid, for these are not readily ab- 
sorbed by the stomach, and they throw additional work upon 
an organ which already empties itself poorly. 46 That the stag- 
nation of food in the stomach directly influences the gastric 
secretion has been proved by the changes in the secretion 47 
which follow drainage of a stomach after a successful gastro- 
enterostomy. 

(Dilatation is therefore one of the most striking, and at 
the same time one of the most serious results of a motor insuffi- 
ciency. Yet the two do not necessarily run a parallel course. 
On the one hand, the gastric motility may be impaired with- 
out any dilatation, while on the other it is possible to have an 
enlarged stomach without motor insufficiency. In the former 
case the stomach empties itself slowly and may even never 
become completely emptied ; yet it does not become distended, 
for the reason that there is an absence of the other factors 
necessary to produce this result, such as the accumulation of 
abnormal amounts of gases, fluids, etc. In the latter case the 
muscular tonus of the stomach is lessened, and the organ 
dilates; yet at the same time it empties itself of food within 
the normal limits of time. 

If large quantities of food or drink are habitually taken, 
the cavity of the stomach becomes enlarged, as has been re- 
peatedly observed in Munich beer-drinkers. This dilatation is 
necessary and of a compensatory nature, and it is usually not 

40 v. Mering, Kongr. f. in. Med., 1893, p. 471 ; Miller, Arch. f. Ver- 
datuingskr., vol. i. p. 233. 

47 Kausch, Mitth. aus d. Grenzgeb., vol. iv. p. 347. 



256 CLINICAL PATHOLOGY 

associated with any motor insufficiency. It may well be com- 
pared to the dilatation of the left ventricle that regularly ac- 
companies a compensated aortic insufficiency (see p. 34). A 
dilatation of this character has an entirely different significance 
from that caused by a relative weakness of the gastric muscu- 
lature. Clinically it is customary to designate the difference 
between the two by calling the former a large stomach (mega- 
logastria) and the latter a true dilatation. — Ed.) 

Causes of Dilatation. — Dilatation may result from a 
variety of causes. In the first place, it may follow a mechani- 
cal stenosis of the pylorus, such as may be caused by tumors, 
contracted scars, or pressure from without. It is quite prob- 
able also that it may follow a spastic contraction of the pyloric 
muscle, which arises from reflexes from ulcers, from sensitive 
spots on the mucosa, or perhaps from the irritation of a normal 
mucous membrane by caustic substances or even by hyperacid 
secretions. 48 

Every stenosis of the pylorus increases the work of the 
muscle in the antrum pyloricum. This additional work causes 
the muscle to hypertrophy just as additional work elsewhere 
will lead to an hypertrophy of the corresponding muscle. The 
more powerful contractions of the hypertrophied gastric muscle 
may for a time neutralize the effects of even a considerable 
stenosis. To what extent this is possible depends upon the 
relation existing between the degree of stenosis and the strength 
of the hypertrophied muscle. Ultimately the hinderance to the 
exit of food may exceed the compensatory power of the 
antrum, and then the stomach will no longer be able to empty 
itself completely. Dilatation then begins, and this dilatation is 
frequently favored by a concomitant weakening of the antrum 
caused by a degeneration of its smooth muscle-fibres. 

Anomalies in the form and position of the stomach may 
also lead to dilatation. Changes in its immediate surroundings, 

48 Riidimeyer, Arch. f. Verdauungskr., vol. vii. 



THE DIGESTION 257 

tight lacing, enteroptosis, — all these exercise a most pronounced 
influence upon the ability of the stomach to empty itself. Such 
conditions may cause, in the first place, an actual narrowing 
of the gastric outlet, as happens, for example, when an abnor- 
mally low stomach presses upon or kinks the duodenum. Then, 
too, the low position of the fundus in gastroptosis increases 
the difference in the level between it and the pylorus, and 
renders a greater amount of work necessary to lift the contents 
out of the stomach. Remarkable acute dilatations 49 sometimes 
follow laparotomy, the stomach becoming enormously dis- 
tended within a few hours. In some of these cases the dilata- 
tion apparently results from an acute obstruction which is 
caused by a kinking of the duodenum. 

In other cases of gastric dilatation no hinderance to the 
exit of food is apparent. Such dilatations have been met with 
in chronic gastritis, ulcer, and carcinoma, in cases of hyper- 
acidity and hypersecretion, and finally in association with 
enteroptosis, neurasthenia, and diseases of the spinal cord. 50 
Some of these should perhaps be classified with those in which 
a functional stenosis exists, for it seems probable that a dilata- 
tion may follow a spasm of the pylorus, such as may accom- 
pany gastric ulcer or marked hyperacidity. In other patients 
mechanical factors of various kinds, such as an abnormally low 
fundus, may have interfered with the motility of the stomach. 
Yet, even after excluding all these, there still remains a group 
of cases for which no mechanical cause can be found and in 
which the dilatation is apparently caused by a primary weak- 
ness of the gastric musculature. Such have been termed 
atonic dilatations. 

By atony is meant a lack of muscular tone. The atonic 
stomach is flaccid and contracts less firmly upon its contents 

48 Fleiner, Verdauungskr., vol. i. p. 352 ; Albrccht, Virch. Arch., vol. 
clvi. p. 285. 

M Kausch, Mittli. a. d. Grenzgeb., vol. vii. 
17 



258 CLINICAL PATHOLOGY 

than does the normal organ. Consequently its cavity tends to 
become distended. The motility of such a stomach may be 
little or not at all impaired, in which case it empties itself 
within the normal period of time. More frequently, however, 
a motor insufficiency is present, and the food remains in the 
stomach longer than it should. (As a rule, this motor in- 
sufficiency is of the milder type, and the stomach does ulti- 
mately empty itself without allowing a continuous stagnation 
of its contents. — Ed. ) 

Finally, gastric fermentation may cause a dilatation of the 
stomach. 51 Fermentation is, of course, a common sequel to 
dilatation, yet in some instances it is primary. In Naunyn's 
cases, dilatation and disturbances of gastric motility resulted 
from the introduction of large numbers of micro-organisms, 
together with easily decomposable food, and the dilatation dis- 
appeared as soon as the gastric contents were removed. The 
abnormal fermentation gave rise to large amounts of gas, 
which would undoubtedly interfere with the movements of the 
stomach. Possibly, also, the acid products of fermentation led 
to a reflex spasm of the pylorus. 

Effects of Motor Insufficiency. — The results of a motor 
insufficiency of the stomach may be very serious. In the first 
place, if the obstruction at the pylorus is nearly complete, the 
patient will die from lack of nourishment, unless a communi- 
cation be established by operative means between the stomach 
and the intestines. If the obstruction is incomplete, but yet 
sufficient to cause considerable stagnation, then favorable con- 
ditions are present for the growth of micro-organisms, and 
various abnormal decompositions will ensue. The presence 
or absence of free hydrochloric acid in the stagnated contents 
is an important factor in determining which micro-organisms 
can develop and what shall be the character of the abnormal 
decompositions. As a rule, an atonic stomach absorbs material 

61 Naunyn, Arch. f. klin. Med., vol. xxxi. p. 225. 



THE DIGESTION 259 

poorly, and the retention of digestive products (albumoses, 
etc.) in the gastric contents will interfere to a certain extent 
with the further progress of digestion. 52 Possibly, also, ab- 
normal quantities of true peptones are formed when the food 
remains in the stomach, and these cause a direct irritation of 
the gastric mucous membrane. Lastly, decomposed material 
and large numbers of bacteria are passed on into the intestines, 
where they may irritate the more delicate membrane and 
initiate further abnormal decompositions. 

Very remarkable nervous symptoms sometimes develop as 
a result of gastric dilatation. 5 ^ Of these we may name the 
fully developed and rudimentary forms of tetany, epileptiform 
convulsions, tonic muscular contractions resembling tetanus, 
and, finally, symptoms of general depression and collapse. 
These symptoms usually occur in cases in which dilatation is 
associated with hyperacid secretion, but the latter is not abso- 
lutely necessary. The cause or causes of these nervous symp- 
toms are not well understood. One is tempted to assume that 
toxic substances are formed in the abnormal fermentations, and 
that these produce the symptoms by their action upon the ner- 
vous system. Indeed, French observers have prepared extracts 
from the stomach contents, and have shown that these may 
give rise to somewhat similar nervous disturbances. 54 Yet 
these experiments need careful confirmation before much 
weight is to be laid upon them. In some patients, no such 
poisons could be found, and Fleiner is of the opinion that 
mechanical causes, such as an overfilling of the stomach with 
a stretching of its parts, may play a more important role in 
the production of these symptoms. 

" Chittenden and Amerman, Jour, of Phys., vol. xiv. p. 483. 

M Kussmaul, Arch. f. klin. Med., vol. vi. p. 471; F. Miiller, Charite- 
Annalen, vol. xiii., 1888, p. 273; ibid., Kongr. f. in Med., 1898, p. 167; 
Ferranini, Ztrbl. f. in. Med., 1901, p. 1 ; Fleiner, Arch. f. Verdauungskr., 
vol. i. p. 243. 

" Bouveret and Dcvic, Revue <lc mldecine, vol. xii. p. 48. 



260 CLINICAL PATHOLOGY 

Belching and Vomiting. — In addition to the normal move- 
ments of the stomach, others may occur which tend to empty- 
its contents in the direction of the oesophagus. Waves of anti- 
peristalsis have been directly observed in cases of gastric dila- 
tation. 55 

By belching, we understand an expulsion of gas from the 
digestive tract through the mouth. Air in the oesophagus 
is easily expelled, for a powerful inspiratory movement with 
a closed epiglottis will draw air into the oesophagus which may 
afterwards be expelled during expiration. The gases may, 
however, come from the stomach, and they then consist either 
of air which has been swallowed, 56 or of gases which have 
arisen from abnormal fermentations, — viz., carbon dioxide, 
hydrogen, and methane. The gas frequently carries with it 
small amounts of liquid into the throat, and if this contains 
fatty acids, as it frequently does in gastric fermentation, it 
gives rise to the burning sensations known as pyrosis. Hy- 
drochloric acid itself may also be carried up, and it will also 
produce unpleasant acid sensations. 

The combination of movements by which the gas is ex- 
pelled consists, on the one hand, of a relaxation of the sphincter 
at the cardiac end of the stomach, and, on the other, of a 
contraction of the abdominal muscles and diaphragm, whereby 
the intra-abdominal pressure is increased. Possibly, in some 
cases, the stomach also assists by contracting upon its contents. 
This complicated mechanism is most frequently set in motion 
by reflexes from the stomach or peritoneum. 

In certain cases, the same movements take the form of 
clonic spasm, and this produces the condition known as hic- 
coughing. Hiccoughing is also incited by reflexes from the 
stomach and peritoneum, but it may furthermore arise from 

55 Cahn, Arch. f. klin. Med., vol. xxxv. p. 402; Rautenberg, Arch. f. 
klin. Med., vol. lxvii. p. 308. 

56 Mathieu, Arch. f. Verdauungskr., vol. x. p. 29. 



THE DIGESTION 261 

causes situated in the central nervous system, as is the case 
in the hiccoughing of hysteria, etc. 

Vomiting is produced by a series of movements of the 
respiratory, abdominal, and gastric muscles, which follow each 
other in a certain sequence, and which finally culminate in 
the expulsion of the contents of the stomach through the 
mouth. Vomiting is initiated by a deep inspiration, which is 
then followed by a spasmodic contraction of the abdominal 
expiratory muscles, during which the glottis is closed and 
the diaphragm is held in a low position. The pyloric orifice 
is tightly contracted, the cardia is relaxed, and the stomach 
itself, though usually relaxed, may possibly perform anti- 
peristaltic movements. During the primary deep inspiration 
some of the gastric contents are probably aspirated into the 
oesophagus, for the circular muscles of this tube are relaxed and 
its longitudinal muscles are contracted. When, finally, the 
abdominal muscles contract, the intra-abdominal pressure is 
raised very greatly, and the contents of the stomach and of 
the oesophagus are expelled through the mouth. 

This complicated mechanism is governed by a special centre 
in the medulla, situated not far from the respiratory centre. 
This " vomiting centre" may be acted upon directly by intra- 
cranial diseases and by poisons, or it may be stimulated re- 
flexly through the vagus fibres from the stomach, especially 
from the terminations of those which supply the neighborhood 
of the cardiac orifice. Vomiting may also be caused by 
reflexes from other organs, especially from the peritoneum, 
uterus, etc. 

The act of vomiting not only affects the stomach but it 
also influences to a marked degree the general blood-pressure 
and the intrathoracic pressure. Traube has shown that at the 
beginning of the act the blood-pressure falls, and that the 
slow pulse is due to a vagus stimulation. Toward the end of 
the act both the blood-pressure and the pulse-rate are greatly 



262 CLINICAL PATHOLOGY 

increased. The salivation and the sweating which occur at the 
beginning of vomiting demonstrate how wide-spread are the 
changes incident to this act. 

Sensations arising from the Stomach. — A healthy man is 
not conscious of his stomach except when he is hungry or 
when the organ is overfilled. The sensation of hunger is un- 
doubtedly dependent to a great extent upon the condition of 
the stomach, though we do not know the exact changes which 
give rise to this sensation. It seems probable that the intes- 
tines also influence the sense of hunger, for patients with intes- 
tinal fistulae have been observed whose hunger was not fully 
satisfied when food was put into the stomach, but was satisfied 
if food material was also introduced into the intestines. 57 The 
mental condition likewise influences the sensation of hunger, 
as is well known. To what extent the needs of the body for 
new material influences the sensation is still uncertain; yet 
these needs do seem to exert some influence, and the hunger of 
diabetes as well as that following muscular exertion seem to 
be examples of " tissue hunger." Of all these various factors 
that may influence hunger the condition of the stomach is the 
most important. 

Abnormally increased hunger is sometimes seen in patients 
with gastric ulcer or in those with hyperacidity, especially 
when there is an accompanying hypermotility of the stomach. 

As a rule, however, gastric disturbances diminish the sen- 
sation of hunger, and the patient then has less inclination 
to take food (loss of appetite). Diminished hunger and loss 
of appetite are not precisely synonymous, for a person may 
say that he is hungry, and yet he will not eat, because he 
" has no appetite" for the food set before him. Loss of 
appetite accompanies many disturbances both of the gastric 
secretion and of gastric motility, but its exact cause is not 
known. 

BT Busch, Virch. Arch., vol. xiv. p. 140. 



THE DIGESTION 263 

The sensations of fulness and pressure, which the healthy 
person experiences only after a full meal, become pathological 
if they are present when the stomach is not much distended. 
These sensations are produced more readily when the dis- 
tention takes place rapidly than when it occurs gradually. 
This would seem to indicate that an increased tension of the 
stomach wall is an important factor in their production. 

Gastric pain is frequently due to ulcerations of the wall 
of the stomach, whether these be round ulcers or are produced 
by carcinomata or -by the action of corrosive poisons. It seems 
very probable that the pain in such cases is caused by the 
irritating action of the acid gastric contents upon the exposed 
base of the ulcer. Indeed, we know the acid may cause most 
intense pain, even when there is no ulceration. In such cases 
the pain may possibly result from a direct irritation of the 
terminals of the sensory nerves in the stomach wall; yet it 
seems more probable that, in most cases, it is due to a muscular 
spasm, more especially of the pyloric or the cardiac orifices. 
The sensations popularly known as cramps in the stomach may, 
therefore, in some instances, be actually due to spasms of the 
gastric musculature. As we have said, such cramps are fre- 
quently caused by hyperacid secretions or by ulcerations. Gas- 
tric pains may, however, be of a neuralgic character, and we 
are as ignorant concerning the nature of these as we are con- 
cerning the nature of neuralgias in general. The terrible pains 
which accompany the gastric crises of tabes and of other spinal 
affections are perhaps due to irritative degenerative processes 
in the pneumogastric nerve. 

Disturbances of the stomach may lead to a great variety 
of symptoms in other parts of the body. We have already 
mentioned the attacks of tetany and related symptoms. There 
may also be various vasomotor disturbances, paresthesias, neu- 
ralgias, migraine, vertigo, as well as disturbances in the inner- 
vation of the heart (irregular action) and of the lungs 



264 CLINICAL PATHOLOGY 

(cough). Some of these symptoms are of a reflex nature, 
others are probably due to poisons absorbed from the stomach. 
The investigation of this latter class of cases promises inter- 
esting results in the future. 

It is especially characteristic of the stomach that disturb- 
ances of its function are combined in the most varied manner, 
and that one disturbance tends to bring others in its train. In 
certain cases it is possible to determine which of these is pri- 
mary and which are secondary. In other cases we cannot make 
such a separation. 

Functional disturbances of the stomach are not accom- 
panied by constant anatomical changes, and the condition 
known as gastric catarrh is especially destitute of any well- 
defined pathological-anatomical basis. The relation between 
functional and anatomical changes in the stomach is not easily 
.studied, because so few gastric disorders are fatal and because 
the stomach changes so rapidly after death. For these reasons 
we know comparatively little about the relation between func- 
tional and anatomical changes in the stomach. 

Not frequently patients complain of loss of appetite, nausea, 
and sensations of pressure in the abdomen, and yet the most 
careful investigation fails to reveal any secretory or motor 
changes. In a certain proportion of these cases it is possible 
that an unusual sensitiveness of the stomach exists, and that 
if the patients are careful in their diet they are relieved of the 
discomfort. In other cases, however, the symptoms seem to 
occur quite independently of the quantity and quality of the 
nourishment, and depend rather upon the psychic state of the 
individual. To this class of cases Leube has given the name 
of nervous dyspepsias. The frequency of nervous dyspepsia 
increases as the resistance of people to the unpleasant things of 
life diminishes. We all know the great influence our minds 
exert upon our digestion, and it is easy to conceive that this 



THE DIGESTION 265 

influence might be pathologically intensified in neurotic indi- 
viduals. Indeed, secretory and possibly even motor functions 
of the stomach may be thus influenced. Strumpell has termed 
such cases psychic dyspepsias. 58 

DISTURBANCES IN THE SECRETION OF BILE. 

We know little of the variations which diseases cause in 
the amount and composition of the bile. Physiological experi- 
ments would seem to indicate that the amount is diminished 
in all those conditions in which but little food is taken. This 
diminution affects especially the water and the bile salts; but 
we are less certain as to the effect of inanition upon the 
bile pigments, for considerable variations in these occur 
normally. 

Substances, not ordinarily present, may appear in the bile. 
Thus when the sugar in the blood exceeds 0.3 per cent., it is 
excreted by the liver, and the same is true of other substances, 
although this is apparently of but little practical significance. 
Albumin is said to appear in the bile in certain diseases. In 
certain others, especially in degenerations of the hepatic cells, 
and in the infectious diseases, the secretion of pigments is 
diminished, yet this occurs only in a minority of the cases. 
Further observations in this field are necessary. 

It is possible to affect the composition of the bile through 
changes in the blood. When large numbers of red blood- 
corpuscles are destroyed, the liberated pigment is taken up 
by the various organs, especially by the liver (p. 141). This 
directly influences the bile. Its quantity at first is diminished, 
the formation of the pigments from the haemoglobin is in- 
creased, and the bile salts are either normal or are diminished. 
Not infrequently the oxyhemoglobin itself passes into the 
bile, 50 even long before it appears in the urine. 

58 Arch. f. klin. Med., vol. lxxiii. p. 672. 

" Filehne, Virch. Arch., vol. cxxi. p. 605 ; Stern, ibid., vol. exxiii. p. 33. 



266 CLINICAL PATHOLOGY 

Certain poisons affect the composition of the bile. Of 
these, we may name toluylendiamin, arsenuretted hydrogen, 
and phosphorus. The first two destroy the red corpuscles of 
the blood, but phosphorus does not do so in mammals. In 
the earlier stages of intoxications with these compounds, the 
total quantity of the bile is usually diminished, the pigments 
are increased, and the bile salts only slightly increased or 
possibly diminished. Owing to an increase in its content of 
nucleoproteids, the bile becomes thick and viscid. In the later 
stages of these intoxications, the bile increases in quantity, 
its composition varying in different ways. These quantita- 
tive and qualitative changes are produced in part by the de- 
structive action of certain of these poisons upon the red 
blood-corpuscles. Yet this is not the only cause of the 
biliary changes. The main factor seems rather to be a 
stimulation of the liver cells to the production of an abnor- 
mal secretion. 

Gail-Stones. — Gall-stones usually originate in the gall- 
bladder. At times only one stone is found; more frequently, 
however, several or many are present. The numerous calculi 
so frequently found in the gall-bladder at autopsy are, in many 
instances, all of about the same size. In other instances they 
occur in groups, as, for example, one or two large, ten or 
twelve medium-sized, and fifty or more tiny stones. Such 
have been termed generations of gall-stones. The explanation 
for this grouping of stones seems to be that during some 
pathological process in the past several nuclei had originated, 
and that when once started the stones tended to act as centres 
about which the bile constituents should deposit. This con- 
tinued until some change in the conditions in the bladder 
allowed a fresh set of stones to start. 

Gall-stones are composed, for the most part, of cholesterin 
and of the calcium salt of bilirubin. Both these substances 
usually enter into the composition of the stone, but some 



THE DIGESTION 267 

stones are composed entirely of one or the other of them. 
Other materials which may be present in biliary calculi are 
calcium carbonate, salts of the heavy metals, pure bile pig- 
ments, and derivatives of these pigments. 

The precipitation of these substances out of the bile is 
not caused by their being produced in the body in abnormally 
large quantities. We know from Naunyn's observations that 
the amounts of cholesterin and of lime salts in the bile is in 
no way dependent upon the character of the food taken or upon 
the general metabolism. Cholesterin is held in solution in 
the bile by the cholates, soaps, and fats. This solution is 
not a saturated one, and cholesterin is not precipitated either 
by evaporating the bile or by allowing it to decompose. Un- 
dissolved cholesterin may be present in the bile, either because 
it has separated out of solution for the reason that the crys- 
tallization point has been reached, or because it has been 
carried into the bile undissolved by desquamated epithelial 
cells. The calcium salt of bilirubin seems to precipitate out 
of the bile only at a certain reaction and in the presence of 
proteids. 

The most important causes which contribute to the pre- 
cipitation of these substances from the bile are stagnation 
and infection. In old age the muscular tissue about the bile 
passages atrophies, and the normal movements of the bile are 
therefore interfered with. In women, lacing and pregnancy 
tend to distort the biliary tract and also to produce stagnation 
by pressure. Heredity seems to play some part in predis-- 
posing to the formation of gall-stones. 

Stasis greatly favors the development of an infection of 
the biliary passages. The normal bile is usually sterile in 
spite of the open communication which exists between the 
common duct and the intestinal tract. 00 The current of flow 
carries foreign material into the intestines, and, even though 
80 E. Fracnkcl and Krause, Ztft. f. Hyg., vol. xxxii. p. 97. 



268 CLINICAL PATHOLOGY 

bacteria are artificially introduced into the bile, they may be 
carried away by the current without their doing any harm. 
On the other hand, a mere ligation of one of the larger bile- 
ducts in an animal often suffices to set up an inflammation. 61 
(The following facts support the view that infections of the 
biliary tract enter by way of the portal vein more frequently 
than by the common duct. Adami and Ford have claimed that 
there is a constant passage of bacteria through the mucosa of 
the healthy intestines; and bacteria introduced into the blood 
may be excreted in the bile (Cushing). The bacteria causing 
a cholecystitis are often not those commonly found in the duo- 
denum. The infection of the biliary passages above a ligature 
around the common duct could hardly come from an ascend- 
ing infection. Finally, if an enteritis be caused by the adminis- 
tration of arsenic, etc., and if the animal then be fed some 
easily recognized organism, such as the bacillus prodigiosus, 
this organism can often be demonstrated in the bile-passages. 
These facts render it very probable that infection of the bile- 
passages frequently takes place by way of the portal vein. 
— Ed.) The bile is apt to contain bacteria in the infectious 
diseases, such as typhoid fever and pneumonia. 

The bacterial infection produces an inflammation of the 
mucous membrane and a desquamation of its epithelial cells. 
These latter contain undissolved cholesterin. They likewise 
contain calcium salts, and these probably react to form the 
insoluble calcium salt of bilirubin. From this salt, as well as 
from the amorphous cholesterin in the cells, the biliary calculus 
takes its origin. Its further growth is carried on by the dep- 
osition and recrystalization of new material, especially of 
cholesterin. 

Several facts favor the view that gall-stones result from 
infectious catarrhs of the biliary passages. Thus bacteria may 
be recovered from the centres of gall-stones, although this 
C1 Homen, Ztrbl. f. Path., vol. v. p. 825. 



THE DIGESTION 269 

is possible only in the minority of cases. Gall-stones have 
also been produced experimentally, by causing biliary stasis 
and by infecting the bile-passages with bacteria of low viru- 
lence. As we have already stated, groups of stones in a gall- 
bladder are frequently of about the same size and presumably 
of the same age, and it may be inferred that they have all 
originated at about the same time from a common cause. In- 
fection of the bile-passages is by no means an infrequent event 
after certain infectious diseases, especially after typhoid fever, 
and it is quite conceivable that this furnished the common 
cause for the formation of a number of stones, and that after- 
wards the bacteria died out of the bile and no new stones were 
formed. 

Cholelithiasis frequently produces no symptoms ; and espe- 
cially is this so when the calculi lie quietly in the gall-bladder 
without occluding any of the ducts. Gall-stones may, how- 
ever, give rise to severe pains, as well as to inflammations, 
peritoneal adhesions, perforations, and septic infections of the 
liver. All of these evil consequences are initiated by an in- 
flammation of the gall-bladder containing the stones. Riedel 
believes that this inflammation may be induced merely by the 
presence of the stone which acts as a foreign body, but that 
in some cases at least it is started by a traumatism. The 
cystic duct is then liable to become occluded either by the 
extension of the inflammation to its mucous membrane or by 
the lodgement of a stone within it. Hydrops of the gall- 
bladder ensues. Its original contents of bile become modified 
by interchange with the lymphatic fluids. The cholates early 
disappear, the pigments follow them, and finally a clear fluid 
is left, which contains salts, cholesterin, neucleo-albumin, and 
characteristic proteids. If bacteria are present, they may 
cause suppuration. The inflamed wall of the gall-bladder 
may ulcerate, it may become adherent to surrounding struc- 
tures, or it may perforate. Not infrequently the stone passes 



270 CLINICAL PATHOLOGY 

through the cystic duct and occludes the common duct. It 
may then produce a variety of inflammatory processes in the 
liver, the peritoneum, the stomach, and the intestines. 

The stagnation of bile and the injury to the walls of the 
biliary passages, both common results of gall-stones, greatly 
favor the development of secondary infections. We have 
already stated that bacteria may enter the common duct from 
the duodenum, but that they probably more frequently de- 
scend from the liver, whither they have been carried by the 
portal blood. The obstruction caused by the stones greatly 
favors the multiplication of bacteria which have thus entered 
the bile, and inflammatory processes of all kinds result. 

Carcinomata sometimes complicate gall-stones, and in such 
cases it is supposed that they" are caused by the irritation of 
the mucous membrane. 

Biliary colic is the most frequent manifestation of chole- 
lithiasis. It is characterized by attacks of violent pain in 
the region of the liver, and is usually accompanied by vomiting, 
fever, and sometimes by jaundice. The paroxysm may last 
for hours or days. The colicky pains are caused by the inflam- 
mation and distention of the tract and by the spasmodic con- 
tractions of the muscle in the gall-bladder and ducts. In a 
certain number of cases the attack is precipitated by the passage 
of a small stone from a wide into a narrow passage, as hap- 
pens at the exit from the gall-bladder or just before the 
entrance into the duodenum. Yet such is not always the case. 
A gall-bladder which contains large stones and which is iso- 
lated by an old occlusion of its duct is not infrequently the 
seat of colic. Indeed, colic may come from a gall-bladder 
which contains no stones and which is merely shrunken and 
surrounded by adhesions. The immediate cause of the parox- 
ysm of biliary colic is frequently an inflammation of the bile- 
passages. This may either drive the stone into a narrower 
portion of the duct, or it may cause the mucous membrane to 



THE DIGESTION 271 

swell about the stone, thus occluding the passage. The fever 
and jaundice that so often accompany biliary colic will be dis- 
•cussed in another place (p. 273). 

The Exclusion of Bile from the Intestines. — The bile may 
be excluded from the intestines by gall-stones lodged in the 
common or hepatic ducts, by tumors growing within them or 
pressing upon them from without, or, finally, by catarrhal in- 
flammations which cause a swelling of the mucous membrane, 
and so occlude the narrower portions of the passages, espe- 
cially the exit of the common duct at the papilla of Vater and 
the smaller bile capillaries within the liver. 

The effect of an occlusion of the common duct varies 
with the site of the obstruction. If the latter be seated high 
up, then bile alone is excluded from the intestines, whereas, 
if it be at the papilla of Vater, the pancreatic juice may also 
be in part or altogether shut off. Experiments upon dogs have 
shown that, when no bile can enter the intestines, the digestion 
and absorption of proteids and carbohydrates proceeds ap- 
proximately in a normal manner, whereas the absorption of 
fats is seriously interfered with; only about forty per cent, of 
the fat taken in the food being absorbed, as compared to the 
normal of ninety per cent. 02 Fr. Miiller has shown that the 
same relations hold good for man. If bile be excluded from the 
intestines, the absorption of carbohydrates is not effected and 
the absorption of proteids is only slightly lessened; whereas, 
on the other hand, from sixty to eighty per cent, of the fat 
taken in the food escapes absorption as compared with the 
normal of from seven to eleven per cent. The "clay color" 
of the stools in these cases is caused partly by the absence of 
bile pigments and partly by the presence of excessive quantities 
of fat. It is difficult to explain the cause of this diminished 
absorption of fat on the theory that the latter is taken up 

M Voit, Beitrage z. Biol., Stuttgart, 1882; Rohmann, Pfliiger's Arch., 
vol. xxix. p. 509, 



272 CLINICAL PATHOLOGY 

from the lumen of the intestines as fine particles. If, how- 
ever, we assume that it is absorbed in a state of solution after 
having undergone hydrolytic cleavage, 63 then the important 
role played by the bile might be in part explained by the fact 
that the cholates are capable of holding large quantities of 
fatty acids in solution. 64 

(The bile may also assist the digestion and absorption 
of fats in other ways. In the first place, the emulsification 
of fats is favored by the presence of bile; and in the second, 
the bile accelerates the fat-splitting action of the pancreatic 
juice eightfold and even more. 65 There appears, therefore, 
to be a sufficient physiological explanation for the effect which 
follows an exclusion of the bile from the intestines. — Ed.) 

Even though the bile be excluded from the intestinal tract, 
it is possible to maintain nutrition by paying sufficient attention 
to the diet, which should, under these circumstances, consist 
mainly of proteids and carbohydrates. If the food contains 
much fat, then the latter undergoes excessive cleavage through 
the action of the pancreatic juice and of the intestinal bacteria. 
The products of this decomposition irritate the intestinal mucous 
membrane, and so may lead to disturbances of its functions. 
For this reason the administration of fats to patients with 
biliary obstruction is not only useless but frequently injurious. 
We are not yet certain what effect the absence of bile exerts 
upon the bacterial decompositions, which normally take place 
in the intestines. The putrefaction of proteids has been found 
to be increased in some instances, 66 whereas in others it has 
been diminished. 67 It is very doubtful if the bile exerts any 
antiseptic action upon the growth of micro-organisms in the 

03 Altmann, His. Arch., 1889, p. 91; Krehl, ibid., 1890, p. 97; Pfliiger, 
Pfliiger's Arch., vol. lxxxviii. pp. 299, 431 ; vol. xc. p. 1. 

"Matthes and Marquardsen, Kongr. f. in Med., 1898, p. 358. 
"Hewlett, Johns Hopkins Bull., January, 1905. 
68 Brieger, Ztft. f. klin. Med., vol. iii. p. 465. 
67 Miiller, Ztft. f. klin. Med., vol. xii. p. 45. 



THE DIGESTION 273 

intestines, for Strasburger 68 found no increase, and even a 
diminution, in the number of bacteria in the faeces in cases of 
complete biliary obstruction. 

Jaundice. — If the lumen of the common duct be obstructed, 
and if the liver cells continue to secrete bile, then the gall- 
bladder and the bile-passages become filled with the secretion, 
the pressure of the bile within them increases, the liver cells 
are forced apart, and the bile is absorbed into the lymphatic 
system or directly into the blood. 69 It thus enters the general 
circulation and permeates all the organs of the body. The 
liver cells may, indeed, resecrete some of the constituents out 
of the blood; yet this has little effect, for, the passage into 
the intestines being obstructed, these constituents are again 
reabsorbed. 

In jaundice the bile pigments are deposited in various 
tissues, and the skin assumes a color which varies from a 
light yellow to a dark green or brown. Whether these dif- 
ferent shades are due to a blending of varying amounts of bile 
pigments with the color of the skin, or whether they arise from 
a conversion of bilirubin into other pigments, has not been 
decided. The jaundice may be visible within a few hours 
after the obstruction has taken place, though usually it does 
not appear for from one to three days. The retained bile 
pigments are excreted by the kidneys and by the sweat-glands ; 
but they do not, as a rule, appear in the tears, the saliva, or 
the gastric juice. 

Of the constituents of the bile which pass into the lymph 
and the blood, the bile salts are of especial interest on account 
of their known toxic properties. During the first few days of 
jaundice they can frequently be detected in the urine, but in 
the later stages they are usually absent. Concerning the qnan- 

08 Strasburger, Ztft. f. klin. Med., vol. xlvi. p. 432. 
°*Gerhardt, Kongr. f. in. Med., 1887, p. 460; Harley, Du Bois' Arch., 
1893, P- 291. 

18 



274 CLINICAL PATHOLOGY 

titative relations of other constituents of the bile, how much 
are formed, how much eliminated in the various secretions, 
and how much are destroyed in the body, we know but little. 

Jaundice may arise not only from an obstruction to the 
flow of bile through the larger passages, but from obstructions 
located in the smaller biliary capillaries. These produce the 
jaundice which may accompany various diseases of the liver, 
such as cirrhosis, carcinoma, cholangitis, and calculi of the 
finer ducts. The development of jaundice is dependent less 
upon the nature of the disease than upon its location, the 
essential factor being an obstruction to the exit of bile. The 
jaundice that so frequently accompanies gall-stones may be 
due to the lodgement of a stone in the common or hepatic 
ducts, or to an associated inflammation of the mucous mem- 
brane. According to Riedel, the latter is the more common. 
Closure of the cystic duct does not ordinarily cause jaundice. 

The resorption of the stagnating bile is influenced not 
only by the degree of mechanical obstruction, but by the 
consistency of the secretion. A thick viscid bile, rich in pig- 
ments, may be reabsorbed even when the obstruction is a com- 
paratively slight one, such as might be caused, for example, 
by a catarrh of the bile passages or by an enlargement of 
degenerated liver cells. The icterus of phosphorus and of 
toluylendiamin poisonings is usually produced in this manner, 
as is that which may accompany snake-bites, pneumonia, pyae- 
mia, septicaemia, and various other intoxications and infec- 
tions. In none of these can a marked obstruction to the out- 
flow of bile be demonstrated. This fact gave rise to the 
theory that the jaundice in such cases does not depend upon 
the changes in the liver, but upon the formation of biliary pig- 
ments in other parts of the body. It is, indeed, possible for 
bilirubin to be formed outside of the liver, for this happens 
in old blood-clots ; yet the amount, thus formed, is very small 
and never produces jaundice. Indeed, we may say that, so 



THE DIGESTION 275 

far as we know, jaundice is always of hepatic origin, and that 
we have no proof that a " hematogenous" jaundice can occur. 
For example, it is impossible to produce jaundice in birds after 
extirpation of the liver. 70 Furthermore, it has been shown 
that jaundice of the typical " hematogenous" type may be 
accompanied by the appearance of the bile salts in the urine, 
a proof that the liver was involved in the condition. 71 That 
these salts may be absent in certain cases proves nothing in 
this regard, for the quantity of bile salts formed under different 
conditions varies greatly, and it is apt to be especially small 
during jaundice. Finally, it has been demonstrated that an 
extensive destruction of red blood-corpuscles may lead to a 
swelling of the hepatic cells, and so to an obstruction of the 
finer bile-passages. 

Many observers incline to the belief that jaundice is always 
due to such an obstruction to the exit of bile, although it 
must be admitted that in many instances the obstruction is 
more or less hypothetical and cannot be demonstrated. An- 
other explanation for these cases has been advanced, — viz., 
that the liver cells pour their secretion directly into the blood 
or lymphatic systems. 72 It is important that more attention 
should be paid to possible changes in the liver cells in these 
cases. 

The cause of the icterus neonatorum which occurs in about 
sixty per cent, of all new-born children is not well understood. 
This much is certain, that it results from the resorption of 
bile ; for not only the pigments, but the bile salts as well, are 
found in the various body fluids. 73 It seems probable also that 
icterus neonatorum is associated with a destruction of the red 



10 Minkowski and Naunyn, Arch. f. cxp. Path., vol. xxi. p. i. 
71 Naunyn, Arch. f. Anat. u. Physiol., 1868, p. 401. 

"Minkowski, Kongr. f. in. Med., 1892, p. 127; ibid., Ergebnisse der 
Path., 1897, vol. ii. p. 705. 

73 Birch-Hirchfeld, Virch. Arch., vol. lxxxvii. p. I. 



276 CLINICAL PATHOLOGY 

blood-corpuscles, for it is especially apt to develop in those 
infants who have had the cord tied late and who have there- 
fore received a larger amount of blood from the placenta. We 
know that jaundice frequently accompanies an increased 
destruction of red blood-corpuscles, as happens in paroxysmal 
hemoglobinuria, but the attempts to produce it experimentally 
by the introduction of haemoglobin have hitherto failed. 
There seems, therefore, to be some other factor present than 
the mere destruction of the erythrocytes. Possibly, as Quincke 
believes, the jaundice of the new-born is due to the resorption 
of bile from the intestines. This theory receives some support 
from the fact that for several days after the birth the blood 
from the intestines may not go through the liver, but may 
pass directly into the general circulation from the portal vein 
by way of the ductus venosus. 

Effects of Jaundice. — The obstruction to the flow of bile 
may cut off this secretion from the intestines, with the results 
which have already been described (p. 271). On the other 
side, the liver cells are affected. They become compressed 
and separated; and, though for a time they may continue to 
perform their functions normally, nevertheless, after a while, 
they suffer both in structure and in function. Areas of necrosis 
and inflammation may appear. 74 These are due in part to the 
toxic action of the bile itself, in part they are due to the infec- 
tions that are so prone to appear in stagnating bile. It is 
impossible to apply the experimental data upon this subject to 
man, because the various animals differ so greatly in the effect 
produced by a stasis of bile upon the liver. 

It is difficult to decide which constituents of the bile pro- 
duce each of the varied general symptoms of jaundice. The 
cholates seem to be the most toxic in their action, although 
recently attention has been directed to the poisonous properties 

74 Beloussow, Arch. f. exp. Path., vol. xiv. p. 200 ; Gerhardt, ibid., vol. 
xxx. p. 1. 



THE DIGESTION 277 

of the biliary pigments. 75 The itching of the skin so fre- 
quently present is apparently due to the deposit of pigment in 
the skin. In the early stages of jaundice the heart's action 
may become slow and irregular, both in force and frequency, 
and the blood-pressure may fall (see p. 84). These symp- 
toms seem to be due to the action of the bile salts, for even 
small doses of sodium cholate stimulate the central endings 
of the vagus nerve, and larger doses act upon the heart itself. 
The convulsions that very rarely occur in the beginning of 
jaundice are also possibly due to the action of the bile salts, 
for the injection of very large amounts of cholates will pro- 
duce convulsions. True cholate intoxication occurs in man 
only when the obstruction to the outflow of bile is complete 
or nearly so, and when the formation of these salts is not 
materially interfered with. It may accompany catarrhal jaun- 
dice, cholelithiasis, and carcinomatous obstruction. Yet the 
cholate symptoms are by no means always present in jaundice 
and often they last only a short time, for the quantity of bile 
salts in the blood varies enormously, and it is usually small 
in the later stages of an obstruction. 76 This is due apparently 
to the fact that the hepatic cells may lose, more or less, their 
ability to produce the bile salts, as well as to the constant 
endeavor on the part of the liver to remove bile salts from the 
blood. For these reasons there are frequently no signs of 
cholate intoxication, even when the jaundice is most profound. 
Other Hepatic Toxaemias. — At times serious toxic dis- 
turbances develop in the later stages of liver disease, and these 
may or may not be accompanied by jaundice. The patient 
becomes stuporous and delirious, and, after a few days of high 
fever and perhaps convulsions, death usually terminates the 
scene. The condition resembles the termination of certain 

15 Stadelmann, Ztft. f. Biol., vol. xxxiv. p. 57. 

70 Yeo and Herroun, Jour, of Physiol., vol. v. p. 116; Stadelmann, 
loc. cit. 



278 CLINICAL PATHOLOGY 

other metabolic diseases, such as the coma of diabetes and 
the uraemia of nephritis. It is very improbable that these late 
toxic symptoms are in any way caused by a resorption of bile, 
for, in the first place, the picture differs from a cholate intoxi- 
cation in the high fever and in the frequency of general con- 
vulsions; and in the second place, diseases of the liver may 
terminate in this manner even though hardly any jaundice is 
present, and even though, furthermore, on account of the ex- 
tensive destruction of hepatic cells, it is probable that only 
Aery small quantities of the bile salts are manufactured. 

A wide-spread degeneration of the liver cells seems to be 
the underlying cause of these toxaemias. The hepatic cells 
are known to perform very important metabolic functions, 
such as the storing of carbohydrates, the formation of urea 
out of ammonium salts, the conversion of toxic aromatic com- 
pounds into the comparatively harmless ethereal sulphates, and 
the disposal of various other poisons absorbed from the intes- 
tines. It may therefore be easily understood how seriously 
the metabolism might suffer when the liver is thrown out of 
function. Possibly the above toxaemias are caused by poison- 
ous compounds which would normally be rendered non-toxic 
in the liver. Of great interest in this connection is the fact 
that geese will frequently die of convulsions after extirpation 
of the liver, if they are fed on a rich nitrogenous diet. 77 The 
same holds true for dogs if an Eck fistula between the portal 
vein and the inferior vena cava 78 permits the blood to flow 
from the intestines directly into the general circulation without 
traversing the liver, under which circumstances the liver cells 
gradually degenerate. Certain symptoms, presented by these 
animals, would seem to be due to the action of carbamic acid. 
If ammonium carbamate be injected into the portal blood of 

" Minkowski, Arch. f. exp. Path., vol. xxi. p. 41. 
78 Hahn, Massen, Nencki, and Pawlow, Arch. f. exp. Path., vol. xxxii. 
p. 161. 



THE DIGESTION 279 

normal animals, it is converted into urea in the liver. In 
animals from which the liver has been extirpated or thrown 
out of function this does not occur, and in them the carbamic 
compounds would be free to produce toxic symptoms. 

The toxaemia associated with extensive hepatic disease may 
also possibly be due to the formation of poisonous compounds 
from the disintegrating liver cells. Finally, some of these 
intoxications are undoubtedly of infectious origin, as is prob- 
ably the case in acute yellow atrophy 79 and in the not infre- 
quent infections of the biliary passages which follow chronic 
obstruction. 

THE PANCREATIC JUICE. 

The complete exclusion of the pancreatic juice from the 
intestines without a concomitant exclusion of bile is extremely 
rare, for the gland usually possesses two functioning ducts. 80 
A closure of both of these is rare, and a total degeneration of 
the secreting glandular parenchyma is likewise very excep- 
tional. By far the most frequent site of a pancreatic obstruc- 
tion is the papilla of Vater, and here not only the duct of 
Wirsung, but the common bile-duct as well, would be closed. 
One can never be certain as to the condition of the duct of 
Santorini in man, for it is normally open in about two-thirds 
of all cases, 81 and it may be closed by a catarrhal process ex- 
tending into it from the duodenum. 

For these reasons we are insufficiently acquainted with the 
results of a simple exclusion of the pancreatic juice from the 
intestines. F. Miiller 82 studied the faeces of several patients 
who had extensive pancreatic degeneration, and found that the 
absorption of carbohydrates in the digestive tract was not at 
all affected by the disease, that the absorption of the proteids 

"v. Noordcn, Pathologie des Stoffwcchsels., p. 275. 

80 Opie, Diseases of the Pancreas, p. 30. 

n Opie, loc. cit. 

"Ztft. f. klin. Med., vol. xii. p. 45. 



280 CLINICAL PATHOLOGY 

was only slightly effected, and that the total quantity of fats 
absorbed was likewise not far from the normal. The cleavage 
of fats in the intestines, however, was considerably diminished ; 
for, of the fat in the faeces, only forty per cent, was found to 
be split into fatty acids and soaps as against the normal of 
about eighty-four per cent. (Others have found that pan- 
creatic disease greatly lessened the absorption of fats from 
the intestines. Thus Weintraud's patient lost from twenty- 
two to twenty-five per cent, of the fat taken in the food, and 
Deucher's two patients lost respectively 52.8 and eighty-three 
per cent, of the fat taken in the food. 83 These losses consider- 
ably exceed the normal of seven to eleven per cent. In regard 
to the extent of cleavage of the fats in the faeces, the results 
have also been somewhat contradictory. While some have 
found, as did Muller, that the cleavage was markedly less than 
normal, others have found but little change. 84 

In some cases of pancreatic disease large quantities of 
nitrogenous material have passed through the intestines un- 
absolved, and the microscopic examination of the faeces has 
shown undigested muscle-fibres in great abundance. In the 
absence of very serious intestinal disease, the presence in the 
stools of large numbers of fat droplets and of an excessive 
amount of undigested meat-fibres is certainly very suggestive 
of an exclusion of pancreatic juice from the intestines. — Ed.) 

The experimental studies of Abelmann have demonstrated 
the serious impairment of absorption which follows the extir- 
pation of the pancreas of animals. 85 About fifty-six per cent, 
of the ingested proteids, twenty to forty per cent, of the car- 
bohydrates, and all of the non-emulsified fats appeared in the 
faeces. Of the latter, from thirty to eighty-five per cent, had 

83 Cited in Schmidt-Strasburger, Faeces des Menches, Berlin, 1901, 
p. 149. 

84 See Schmidt-Strasburger, loc. cit. 

85 Abelmann, Diss. Dorpat. 



THE DIGESTION 281 

undergone cleavage into fatty acids and soaps. If the fat were 
introduced in the form of a natural emulsion, such as milk, 
then a considerably larger proportion, about thirty to fifty 
per cent., was absorbed by the intestines. Other experimenters 
have obtained quite different results; in many cases the fat 
was not absorbed at all, and in others up to eighty per cent, 
was absorbed. 86 It seems to me that the results of these ex- 
periments cannot be applied directly to human pathology for 
extirpation of the pancreas is attended with considerable shock 
to the animal and we have no data as to how the secretion of 
bile is influenced by these operations. The metabolism of car- 
nivora should be studied after the pancreatic ducts have been 
tied. The fact that the administration of the pancreas of a 
pig to these animals increases the absorption of food would 
seem to indicate that the absence of pancreatic secretion is the 
main cause of their insufficient absorption. 

(Fat Necroses. — In many pancreatic diseases, peculiar 
opaque, whitish spots have been noticed, which were most 
numerous in the immediate vicinity of the pancreas and beneath 
the peritoneum, but which may also be found in other distant 
parts of the body. These whitish spots are caused by a de- 
composition of the fat in the adipose tissue into fatty acids 
and glycerin. The latter, being soluble, can be washed away; 
whereas the fatty acids are deposited in typical needles, which 
later, combining with calcium, give irregular granular masses. 87 
This abnormal cleavage of fat in the tissues appears to be due 
to the escape of pancreatic juice from the pancreas, for the 
injection of pancreatic extracts into the tissues has been fol- 
lowed by typical fat necroses, and the ordinary fat necroses 
contain a fat-splitting enzyme in greater quantity than docs 
normal fatty tissue. Ks Indeed, this enzyme may even appear 

* See Oser in Nothnagel's system. 

" Langcrhans, Virch. Arch., vol. exxii. p. 252. 

8 * Flexner, Jour, of Exp. Med., vol. ii. p. 413. 



282 CLINICAL PATHOLOGY 

in the urine after extensive experimental destruction of the 
pancreas. 89 

Fat necroses are usually most numerous in those condi- 
tions in which a rapid destruction of pancreatic tissue has taken 
place, as in acute hemorrhagic pancreatitis. They are also 
frequently quite numerous after obstruction of the pancreatic 
duct. Finally, a few small necroses may not infrequently be 
found within the tissues of the normal pancreas. Yet, so far 
as we know, extensive necroses do not occur without there 
being some lesion of this gland. 

Relation of the Bile to Pancreatic Disease. — Owing to the 
fact that the common bile-duct and the main pancreatic duct 
usually open in common into the diverticulum of Vater, which 
latter then opens into the duodenum, it is possible for the 
bile to enter the pancreas directly from the common duct 
when the exit into the duodenum is obstructed. Such an 
obstruction has been produced by a small gall-stone, which 
was large enough to close the opening into the intestines, yet 
small enough not to fill up the diverticulum completely. 90 Bile 
is certainly very irritating to the pancreas, and its entrance 
into that gland may be followed by an acute hemorrhagic 
inflammation. 91 In other cases, when the irritation is less 
marked, a chronic pancreatitis may result. — Ed.) 

THE PROCESSES IN THE INTESTINES. 

The Effect of Poisons upon the Intestines. — The intes- 
tines may be injured by various substances, such as the 
fatty acids, the metallic salts, aromatic compounds, etc. Many 
of these are used therapeutically, while others may be taken 
in the food. It is not easy to separate those which are toxic 
from those which are not, for the susceptibility of different 

*' Hewlett, Jour, of Med. Research, vol. ix. p. 277- 

90 See Opie, Diseases of the Pancreas, p. 40. 

81 Opie, Johns Hopkins Hosp. Bull., vol. xii. p. 182. 



THE DIGESTION 283 

individuals varies enormously in this respect. Even such a 
marked poison as arsenious acid, which in most men causes a 
violent enteritis, may become comparatively harmless through 
habit, and quantities may then be borne which would ordi- 
narily be almost immediately fatal. 

Toxic substances may be elaborated outside the body by 
the action of bacteria. These include the so-called ptomaines, 
many of which, such as neurin, mydalein, and mytilotoxin, 
are extremely poisonous. 92 Since such compounds are only 
formed in the later stages of putrefaction, an intoxication from 
this source is most apt to follow the ingestion of decomposed 
food. Some of these poisonous substances injure the wall 
of the intestines, producing anatomical and functional dis- 
turbances, while others are absorbed and produce more general 
symptoms. 

(Specific toxins, elaborated by specific bacteria, may be 
introduced with the food. The poisonings which sometimes 
follow the ingestion of milk, cheese, and meat seem to be of 
this character. A specific meat intoxication, so-called botu- 
lism, has been shown to be caused by the toxin formed by a 
definite anaerobic bacillus, 93 and an antitoxin has been pro- 
duced which will neutralize its effect. — Ed.) 

It is often difficult to determine whether a certain intoxi- 
cation resulted from poisons introduced with the food, or 
whether it arose from toxins which were produced within the 
intestines by the abnormal action of bacteria; yet in some 
instances the former is by far the more probable, for the symp- 
toms appear almost immediately after the ingestion of the 
decomposed food. The same is also true when the intoxication 
is caused by cooked material, for it is then very improbable that 
any living organisms other than spores were introduced. 

" Brieger, Ueber Ptomaine, Berlin, 1885-86; Neumeister, Physiol. 
Chem., second edition, p. 268. 

M Van Ermengen, Ztft. f. Hyg., vol. xxvi. p. 1. 



2S4 CLINICAL PATHOLOGY 

Abnormal Bacterial Processes within the Gastrointes- 
tinal Tract. — Numerous bacteria are regularly carried into 
the stomach with the food. A portion of these are there de- 
stroyed, some are reduced in virulence, and a part passes on, 
but slightly injured, into the duodenum. When many bac- 
teria reach the intestines, some may decompose the carbo- 
hydrates or split the fats, thus producing organic acids even 
in the small intestines. To what extent the proteids undergo 
putrefaction in the upper intestines under pathological con- 
ditions is not known. In the lower ileum, and especially in 
the colon, the bacterial decompositions normally become more 
marked, and here the putrefaction of the proteids is a normal 
process. 

The number of bacteria in the human intestines varies 
greatly. 94 The dried faeces of a healthy man are made up of 
about one-third, by weight, of bacteria. Yet the upper small 
intestines in fasting animals, at least, are almost free of micro- 
organisms, 05 and it seems very probable that they regulate 
their bacterial flora to a certain degree. 

Certain factors seem to inhibit bacterial growth in the 
small intestines. As we have seen, the hydrochloric acid of 
the stomach diminished the number of bacteria present in the 
food, and it is probable that the bile acids, the fatty acids pro- 
duced by cleavage of the fats, and the intestinal secretions 
themselves exert a certain antiseptic action in the upper intes- 
tines. Of greater importance, however, is the rapid transit 
of material through the duodenum and ileum, and the few 
hours that food remains there does not allow sufficient time for 
the bacteria to multiply. Fortunately, in the large intestines, 
where the transit is slower and where the bacterial action is 

04 Strasburger, Ztft. f. klin. Med., vol. xlvi. p. 413; vol. xlviii. p. 491. 

85 Kohlbrugge, ref. in Baumgarten's Jahresber., 1901, 895 ; see, also, 
Cushing and Livingwood, Contributions to the Science of Medicine, by 
the pupils of Dr. W. H. Welch, Baltimore, 1900, p. 543. 



THE DIGESTION 285 

most marked, the greater portion of nutritive material has 
already been absorbed, and the bacteria have less to decompose. 

Another protection against the growth of strange bacteria 
in the intestines is the inhibitory action which the normal flora 
seems to exert upon the growth of outsiders. 06 For this reason 
the normal flora of the intestines is probably very useful. 
Whether it is absolutely necessary or not, has received different 
answers from different investigators. 97 Guinea-pigs may be 
reared upon sterilzed milk, but a similar attempt with chickens 
has failed, which fact appears to support the view that the 
presence of micro-organisms in the gastro-intestinal tract is 
necessary during extrafetal life. 

The kind of micro-organisms in the intestines depends 
partly upon the food taken, and partly upon the general con- 
dition of the individual. The intestinal contents of a new- 
born infant are sterile, but after birth they quickly become in- 
fected, and at the end of the fourth day a fully developed 
intestinal flora is present. The latter varies with the kind of 
food used, whether mother's or cow's milk, and it varies with 
each change in the food in later life. 

So long as the epithelium remains intact and healthy the 
body is fairly well protected from invasion by the bacteria 
which happen to be present in the intestines. 98 The epithelial 
cells form a protective bulkhead, and their antibacterial action 
is attributed by some authors to their content of nucleinic acid 
nnd its combinations, which substances are acid in reaction 
and will cause a precipitation of proteids." Yet the protection 

M Bienstock, Die med. Wochcns., 1901, Nos. 33 and 34; ibid., Annales 
de I'Institut Pasteur, vol. xiv. p. 750; Arch. f. Hyg., vol. xxxrx. p. 390. 

m Thicrfelder and Nuttall, Ztft. f. phys. Chem., vol. xxi. p. 109; vol. 
\\ii. ]). 62; Schottelius, Arch. f. Hyg., vol. xlii. p. 48; Metschnikoff, 
Annales Pasteur, 1901, p. 631; ECijanitzka, Virch. Arch., vol. clxii. p. 515. 

"* Schott, Ztrbl. f. Bactcriol., vol. xxix. I. pp. 239, 291. 

" Klcmpercr, Deut. med Wochenschr., 1894, No. 20; H. and A. Kossel, 
Du Bois' Arch., 1894, p. 200. 



286 CLINICAL PATHOLOGY 

afforded to the body by the intestinal mucosa is not an absolute 
one. Apparently the tubercle bacillus may penetrate the intact 
mucous membrane, and slight lesions will certainly render the 
epithelium permeable to many bacteria. 100 

The soluble products of bacterial action frequently pass 
through the normal mucosa, and in doing so they may possibly 
render an important service to the individual by immunizing 
him against the action of the bacteria from which they are 
derived. Those toxins which are of a proteid nature may 
in many cases be digested in the intestines, just as are other 
proteids; yet it would appear that this does not occur in the 
intestines of infants. 101 

Many intestinal diseases, perhaps the majority of them, 
are due to abnormal bacterial action within the intestines. The 
bacteria ordinarily present may increase in number or in 
virulence, or bacteria that are not usually present may give 
rise to pathological changes. Such foreign micro-organisms 
must of course be introduced from without, and it is mani- 
festly impossible, for example, to acquire cholera at a time 
when no cholera bacilli are about. The mere introduction of 
pathogenic bacteria does not, however, necessarily do any 
harm; for just as large numbers of harmless bacteria daily 
enter the gastro-intestinal canal and there disappear, so may 
pathogenic organisms be destroyed without their producing 
any ill effect. They succumb to the various protective agencies 
in the stomach and intestines that have already been described. 
In some cases, however, the bacteria introduced are so numer- 
ous or so virulent that they cause the disease in practically 
every individual in whom they enter, as is illustrated by the 
fact that every person who has partaken of a particular dish 
may become ill from it. 

It is often impossible to say in what manner the infection 

100 Posner and Cohn, Berl. klin. Wochenschr., 1900, No. 36. 

101 Behring, Naturforscher-versammlung zu Kassel, 1903. 



THE DIGESTION 287 

has taken place, whether it is by overcoming the normal in- 
habitants of the intestines, or by causing a lesion of the mucosa, 
etc. Apparently different factors enter into consideration in 
different infections. We know, for example, that the cholera 
vibrio is extremely sensitive to the acid reaction of the gastric 
juice, and clinical experience has shown that the disease is 
especially apt to attack individuals who have presumably a 
lessened gastric acidity, caused either by some slight digestive 
disturbance or by great fear of contracting the disease. 

Intestinal indigestion is apt to be produced in some in- 
dividuals by certain articles of diet, and it is quite possible 
that these articles allow the bacteria normally present in the 
intestines to proliferate with abnormal rapidity, or that they 
reduce the resistance which the flora of the intestines normally 
exerts against foreign invaders. In some cases, however, they 
cause the indigestion by directly influencing the secretions 
poured into the intestinal canal. The first of these possibilities 
seems to be exemplified in the case of infants, for in them 
some very slight qualitative or quantitative change in the 
food may induce a dangerous proliferation of bacteria, quite 
independently of the bacterial contents of the food ingested. 

On the other hand, the abnormal bacterial growth may 
follow changes in the secretory or motor functions of the intes- 
tines. The normal emptying of the faeces is one of the most 
important means by which abnormal bacterial growths are 
limited, and changes in the secretions are perhaps of equal im- 
portance. 

How frequently the normal inhabitants of the intestinal 
tract produce disease has not yet been fully determined. It is 
certain that they may give rise to a peritonitis when the bowel 
ruptures or when its wall becomes abnormally permeable, as 
happens in strangulation. Local infections may take place 
when the intestinal wall is injured, and this is the probable 
cause of many a colon bacillus cystitis. Beyond this we know 



288 CLINICAL PATHOLOGY 

little about such enterogenous autoinfections. 102 (Generalized 
infections with the colon bacillus have, however, been fre- 
quently demonstrated by blood-cultures. — Ed. ) Possibly some 
of the infantile diarrhoeas are caused by a change in virulence 
in the normal intestinal flora. (These diarrhoeas are now 
believed to be produced by infections with the dysentery 
bacillus, although the question as to whether such bacilli may 
be normal inhabitants of the intestines or not has not yet been 
fully determined. 103 — Ed.) 

An abnormal growth of bacteria in the intestines may 
harm the body in several ways. Either the poisons formed 
may be absorbed and cause a general toxaemia, or they may 
act directly upon the mucosa itself, and so interfere with its 
functions. Frequently the mucosa undergoes anatomical altera- 
tions, such as degenerations of the epithelium, inflammations, 
and ulcerations. These latter are important, for when they 
occur, the barriers to invasion are let down and bacteria may 
penetrate the mucosa and cause a general infection. 

Various toxic compounds result from bacterial decompo- 
sitions in the bowel. Of these, some, such as lactic acid, 
butyric acid, and acetic acid, have already been mentioned in 
speaking of the abnormal fermentative processes in the stom- 
ach. These acids are regularly produced in the small intestines, 
but under pathological conditions the quantity so produced 
may be enormously increased. They irritate the intestines, 
increase the peristaltic movements, and may cause lesions of 
the epithelium. Gases, such as hydrogen, carbon dioxide, and 
methane, likewise may be produced in excessive quantity and 
cause tympanites and intestinal colic. 

An excessive proteid decomposition in the intestines gives 
rise to all the various products of putrefaction, among them 

102 F. Miiller, Kongr. f. in. Med., 1898, p. 156. 

103 Studies from the Rockefeller Institute for Medical Research, vol. ii., 
1904. 



THE DIGESTION 289 

indol, skatol, phenol, and other compounds belonging to the 
aromatic series of compounds. Many of these are rendered 
non-toxic after absorption, through combination with sulphuric 
acid, glycocoll, glycuronic acid, etc. These combinations ap- 
parently take place in the liver, and the compounds, thus 
formed, are excreted by the kidneys. These aromatic bodies 
are normally formed almost exclusively in the large intestines. 
Their amount depends upon a variety of factors, of which the 
most important are the quantity of material in the chyme 
that can undergo putrefaction, the amount of substances pres- 
ent which will exert an antiseptic action, the varieties of bac- 
teria present, and the rapidity with which the material passes 
through the intestines. 

(Our best index of the amount of putrefaction which is 
taking place in the intestines is the quantitative determination 
of the ethereal or aromatic sulphates in the urine; for, as has 
been said, the aromatic products of putrefaction are largely 
eliminated as such sulphates, when once they have been ab- 
sorbed from the intestines. In this regard, it is important to 
know not only the absolute amount of these ethereal sulphates 
in the urine, but also the ratio which this amount bears to that 
of the ordinary, preformed, inorganic sulphates. In fact, this 
ratio is regarded by most authors as a better index of the 
amount of putrefaction than is the absolute quantity of ethereal 
sulphates excreted. In adults, on a mixed diet, the ratio of 
the ethereal to the preformed sulphates in the urine varies 
from about I : 10 to I : 16, while under pathological condi- 
tions this ratio may become I : 7 or 1:5, or even to 1 : I. 104 
Ethereal sulphates may, however, be formed by putrefactive 
processes outside of the intestines, especially when there is 
suppuration without free drainage, and they may also arise 
from certain drugs of an aromatic nature, such as benzosol, 
salol, salophen, creosote, etc. 

"'Sec Herter, Lectures on Chemical Pathology, p. 202. 
19 



290 CLINICAL PATHOLOGY 

The mere ingestion of a large amount of material that can 
putrefy — e.g., a. large meat meal — is apt to be followed by an 
increase in the absolute and relative quantities of the ethereal 
sulphates in the urine. A similar increase is often observed 
in catarrhal enteritis. The greatest increase, however, follows 
stasis of material in the intestines. Ordinary constipation is 
often associated with a more or less marked increase, and 
intestinal obstruction is regularly associated with the elimina- 
tion of large quantities of ethereal sulphates in the urine. 

We do not know how serious the absorption of these 
aromatic bodies from the intestines is. Indol, when admin- 
istered by mouth, is only moderately toxic, and individuals 
vary considerably in their susceptibility to its action. Small 
doses are liable to produce frontal headaches and a condition 
of nervous irritability and restlessness, larger doses may cause 
diarrhoea, or marked irritability, insomnia, and mental rest- 
lessness. The continued administration of enough indol to 
cause a constant and decided reaction for indican in the urine 
is capable of inducing neurasthenic symptoms. 105 It is very 
probable therefore that the neurasthenia which is so often 
seen in cases of chronic intestinal indigestion is in part due to 
the absorption of the aromatic products of putrefaction. — Ed.) 

It is also possible that the nephritis which so frequently 
follows intestinal obstruction is caused by the products of in- 
testinal decomposition. 106 

Other poisons of a more complex nature than those we 
have just mentioned may play an important role in some cases 
of intestinal intoxication. 107 Apparently ptomaines are not 
formed in the intestines very frequently, and in most infectious 
diseases they do not appear in the urine, 108 yet they have been 

103 See Herter, loc. cit., p. 212. 

108 Frank, Berl. klin. Wochens., 1887, No. 38. 

107 See Kongr. f. in. Med., 1898. 

108 Baumann and Udranszky, Ztft. f. phys. Chem., vol. xiii. p. 562. 



THE DIGESTION 291 

stro-enteric disturbances. (Cholin is one 
of the decomposition products of lecithin, and under certain 
circumstances it may be transformed into the highly toxic sub- 
stance, neurin. Nesbitt has shown that if dogs with an intes- 
tinal obstruction be fed upon the yolks of eggs, rich in lecithin, 
then neurin and cholin may be found in the intestinal con- 
tents, 109 and it is possible that the same may occur in certain 
pathological conditions in man. Perhaps the toxic symptoms 
which sometimes follow the eating of eggs are caused by 
neurin. — Ed.) Cystinuria is regularly accompanied by the 
excretion of the ptomaines, putrescin and cadaverin, in the 
urine and faeces. In general, however, it would appear that 
the food does not remain a sufficiently long time in the intes- 
tines for ptomaines to be formed. 

Toxic intestinal disturbances may arise finally from pro- 
teid-like substances and from other compounds of a totally 
unknown composition. 110 The nature of these is but little 
known, and in recent times it has been questioned whether 
any of them are true proteids. 

Many disturbances in the function of the intestines have 
been ascribed to the action of protozoa, though their etiological 
relationship has been well established for only one disease, 
endemic dysentery. 111 The virulence of the amoeba of dysen- 
tery for cats leaves us in no doubt as to its pathogenicity. Yet 
not all cases clinically classified as dysentery are due to the 
action of this amoeba. 

The Pathology of Absorption. — Absorption takes place 
throughout the small intestines, being more rapid for organic 
substances at least, in the upper than in the lower portion. 

100 Nesbitt, Jour, of Exp. Med., vol. iv. p. n. 

"'Brieger and Fraenkel, Berl. klin. Wochens., 1890, No. II J Neu- 
meister's Physiol. Chem. 

111 Councilmann and Lafleur, Johns Hopkins Hosp. Rep., vol. iii. ; 
Kartulis in the Nothnagel System. 



292 CLINICAL PATHOLOGY 

According to the most trustworthy observations, but little 
nutritive material is absorbed by the large intestines. 

The manner in which many diseases of the intestines affect 
the absorption of food is not fully known. Those circulatory 
disturbances that produce a slower blood-current lead to a dim- 
inution in the absorption of fats, but do not affect the absorp- 
tion of the sugars and proteids. 112 Fat absorption is also re- 
duced whenever the lymphatic vessels that drain the intestines 
are obstructed, as may happen in tuberculosis of the mesenteric 
glands. The diseases that affect the intestines only in isolated 
areas, such as tuberculosis and typhoid fever, have almost no 
influence upon absorption. 113 On the other hand, wide-spread 
diffuse diseases of the mucosa, such as enteritis and amyloid 
degeneration, will diminish the fat absorption if they are 
moderately severe, and will reduce the absorption of all kinds 
of food if they are very severe. This loss of material is caused 
partly by the changes in the mucosa itself and partly by the 
rapid passage of the food through the intestinal tract, though 
diarrhoea alone does not necessarily diminish absorption. 114 

In the healthy individual, the greater part of the water 
in the food is absorbed in the upper small intestines. 115 If 
the amount of water in the faeces be increased, this may arise, 
first, from a diminished absorption of water from the food, due 
either to the presence of salts or other bodies which raise the 
osmotic tension of the intestinal contents, or to a too rapid 
passage of the chyme through the intestines. A rapid transit 
of material through the large intestines always diminishes the 
absorption of water. Drinking large amounts, on the other 
hand, frequently has no effect upon the faeces. 

112 F. Muller, Kongr. f. in. Med., 1887, p. 404 ; ibid, Ztft. f. klin. Med., 
vol. xii. p. 45 ; Grassman, Ztft. f. klin. Med., vol. xv. p. 183. 

113 Muller, loc. cit. ; Hosslin, Virch. Arch, vol. lxxxix. pp. 95, 303. 

114 Dapper, Ztft. f. klin. Med, vol. xxxi. p. 382. 

116 v. Mering, Mortiz, Kongr. f. in. Med, 1893, p. 471. 



THE DIGESTION 293 

In the second place, an increase in the amount of water 
in the faeces may result from excessive secretion. We know 
that the stomach secretes water readily and there is abundant 
reason to believe that the intestines may likewise furnish 
large quantities of fluid to their contents, either by the process 
of transudation or by that of secretion. The most remarkable 
example of watery faeces is furnished by the " rice-water" 
stools of Asiatic cholera. These contain only a trace of 
albumin, an amylolytic enzyme, and hardly any salt except 
sodium chloride. 116 Their composition approaches that of the 
normal intestinal secretion, differing from an ordinary inflam- 
matory exudate in the low proportion of proteids present and 
in the amylolytic ferment. Cohnheim, therefore, believed that 
the rice-water stools of cholera were caused by an increase in 
the intestinal secretions, rather than by an inflammatory exu- 
dation. Yet later researches have shown that the essential 
pathological process in cholera is an intense inflammation of 
the mucous membrane, so that the question as to the inflam- 
matory or secretory nature of the fluid still remains unsettled. 

(Another example of watery stools caused by an exces- 
sive secretion of fluid is furnished by the fluid faeces which 
follow the use of saline cathartics. The watery character of 
these faeces is due very largely to the stimulation of intestinal 
secretion which results from the absorption of the cathar- 
tics. 117 — Ed.) 

Disturbances in the Intestinal Movements. — In discussing 
this subject, it is necessary to consider separately the small and 
the large intestines, for the peristaltic movements in each are 
quite different. 118 During complete fast, rest prevails through- 
out the entire gastro-enteric tract, whereas digestion leads to 
peristaltic movements of the small intestines. These consist, 

""Kiihne, Berl. klin. Wochenschr., 1868, p. 170. 

117 J. B. MacCallum, Am. Jour, of Physiol., vol. x. pp. ioi, 259. 

"" See Magnus, Pfliiger's Arch., vol. cii. pp. 123, 349. 



294 CLINICAL PATHOLOGY 

in the first place, of progressive waves of contraction which 
affect the circular muscle over a limited area, and which travels 
forward, tending to carry the chyme with them. The second 
form of movement is produced by a simultaneous contraction 
of the circular and longitudinal fibres, and this results in a 
twisting of the intestinal coils, which tends to bring different 
parts of the chyme in contact with the mucosa. (Cannon de- 
scribes a third movement, — rhythmical segmentation. At 
regular intervals simultaneous constrictions in the lumen of 
the small intestines take place, and these then again relax. 
These movements occur about thirty times to the minute in 
cats. They persist during sleep, but are checked by violent 
emotions. According to the same author, the most frequent 
movements in the large intestines of cats are waves of anti- 
peristalsis, which begin near the rectum and terminate at the 
ileo-caecal valve. Ordinarily these waves pass for a short time 
at the rate of about five a minute, and then a period of rest 
lasting about ten minutes intervenes. These antiperistaltic 
waves cause the contents of the large intestines to be thor- 
oughly mixed. 119 — Ed.) 

Defecation is a partly voluntary, partly reflex act, which is 
initiated by the presence of more or less faeces in the rectum. 
In many individuals defecation occurs regularly at the same 
time each day, while in others it occurs very irregularly. In 
diarrhoea, the large intestines fill rapidly and frequently with 
fluid contents, and their peristaltic movements are increased. 
The small intestines, however, may or may not be affected. 
The milder and more transitory diarrhoeas usually do not 
involve the small intestines, as may be inferred from the char- 
acter of the faeces. On the other hand, in many conditions, 
such as typhoid fever, the small intestines are affected and 
the stools contain undecomposed biliary pigments and ab- 
normal quantities of unabsorbed food material. Finally, a 
119 Cannon, Am. Jour, of Physiol., vol. vi. pp. 123, 249. 



THE DIGESTION 295 

catarrh may involve the small intestines almost exclusively, in 
which case it may or may not be accompanied by a diarrhoea 
and may even be associated with constipation. 

Nervous Diarrhoeas. — The cause of the diarrhoea may lie 
outside of the intestines. In many individuals a mere cooling 
of the skin or a feeling of nervousness will produce diarrhoea 
without necessarily disturbing the general health. A gradual 
transition may be seen in such cases from the physiological 
to the pathological ; in the one, a pronounced stimulus is 
necessary to produce any effect, whereas, in the other, a little 
excitement or even the fear of a diarrhoea may be enough to 
bring it on. Such individuals often show other neurasthenic 
or hysterical stigmata. It seems probable that their central 
nervous system affects the peristalsis of the intestines through 
the vagus and splanchnic nerves. Even normally, the peri- 
staltic movements are influenced to a certain extent by the 
central nervous system, and in these pathological conditions 
this influence is greatly exaggerated. In some of these cases, 
however, the irritability of the intestines themselves may pos- 
sibly be increased so that they respond excessively to normal 
stimuli. 

Diarrhoeas may accompany anatomical diseases of the ner- 
vous system, as happens, for example, in the intestinal crises 
of tabes. It is quite certain that in these cases the diarrhoeas 
are dependent upon changes either in the nerves or in the cen- 
tral nervous system; yet definite proof of this is wanting. 

In hysterical girls the small intestines are frequently the 
seat of increased peristalsis, often giving rise to constant 
gurgling sounds, without, however, causing any diarrhoea. 
That these peristaltic movements are dependent upon mental 
influences is supported by the fact that they are most liable to 
occur at the very times at which the patient wishes to suppress 
them. 

The watery character of the faeces in nervous diarrhoeas 



296 CLINICAL PATHOLOGY 

may be due in part to the rapid transit of material through 
the intestines, though it seems probable that it is more often 
caused by a nervous hypersecretion from the intestinal mucosa, 
a condition which would find an analogy in the well-known 
instances of nervous secretion of saliva, gastric juice, and 
urine. When the hypersecretion affects the large intestines, 
the mucus and proteids in the secretion 120 may form tubular 
and membranous casts, which are afterwards passed in the 
faeces. This disease, known as colica mucosa (membranous 
colitis), has, in most instances at least, nothing whatever to 
do with an inflammation of the mucous membrane, 121 but is 
a pure secretory neurosis. It usually occurs in nervous 
women, and may be accompanied by the most violent parox- 
ysms of colic. At times, very similar membranous structures 
result from true inflammatory processes in the intestines. 

Diarrhoeas in General Diseases. — Intermediate between 
these diarrhoeas of nervous origin and those due to causes situ- 
ated within the intestines, is a second group, — viz., those that 
accompany general diseases. Several possibilities suggest 
themselves as to the cause of this class of diarrhoeas. In the 
first place, the general disease may so weaken the resistance of 
the intestinal mucosa that the latter falls a prey to the normal 
flora of the intestines or to bacteria which are introduced 
into the gastro-intestinal canal, either by mouth or by the 
secretions from the infected body. In the second place, toxins 
produced by the general disease may directly cause the diar- 
rhoea, just as other poisons do. Some infectious diseases, 
such as pneumonia, rarely cause diarrhoea; whereas others, 
such as measles, frequently do so. Diarrhoea not infrequently 
complicates chronic nephritis. 

Diarrhoeas of Intestinal Origin. — The third and most im- 
portant class of diarrhoeas are those caused by the excessive 

120 Kitagawa, Ztft. f. klin. Med., vol. xviii. p. 9. 

121 Nothnagel, Diseases of the Intestines, in his System. 



THE DIGESTION 297 

stimulation of the intestinal mucosa by the intestinal contents. 
The materials which act as stimulants are, in the first place, 
coarse, hard food remnants, especially cellulose, which resist 
the action of the intestinal secretions and bacteria. In the 
second place, and more commonly, the peristalsis is excited 
by chemical irritants, which may either be introduced from 
without or be produced within the intestinal canal. Of these, 
we shall only name the organic acids and the gases which 
result from fermentation. 122 These are of the greatest im- 
portance in the production of many diarrhoeas. Whether or 
not water alone will increase the peristalsis has not been 
definitely settled. We know, however, that diseases which 
interfere with the absorption of water by the small intestines 
may lead to diarrhoea, as is the case with amyloid degeneration 
of the intestines and with the saline cathartics. (Recent work 
has shown that the saline cathartics act not so much by prevent- 
ing the absorption of water from the intestines as by directly 
stimulating its motor and secretory functions. To do this, the 
cathartic must first be absorbed, and they have been shown to 
be especially efficient when they are injected directly into the 
animal's blood, or when they are painted over the peritoneal 
covering of the intestinal wall. 123 — Ed.) 

Diarrhoea is favored by an increased irritability of the 
intestinal mucous membrane, muscle, or nerves, for normal 
stimuli then give rise to excessive responses. Such an in- 
creased irritability of the intestines is probably present in most 
acute inflammations of the mucous membrane. In acute en- 
teritis, for example, the diarrhoea is due to the combination of 
two causes, increased intestinal irritability and increased 
stimulation of the intestines by the products of abnormal fer- 
mentations. In chronic enteritis there is frequently no in- 
crease in the irritability of the mucous membrane. Even in 

ia Bokai, Arch. f. exp. Med., vol. xxiii. p. 209, and vol. xxiv. p. 153. 
123 MacCallum, Am. Jour, of Phys., vol. x. pp. 101, 259. 



298 CLINICAL PATHOLOGY 

intestinal ulcerations the irritability may not be increased, 
which is especially true of the chronic ulcerations. 

The effect of diarrhoea upon the body depends to a great 
extent upon its cause. If the food is hurried through the 
upper part of the small intestines, its absorption may be seri- 
ously interfered with and the patient may suffer from malnu- 
trition. On the other hand, when the diarrhoea is due entirely 
to an increased peristalsis of the large intestines, it is often 
surprisingly well borne, for the most nourishing part of the 
food had already been absorbed before the large intestines were 
reached. Other associated conditions, however, may render 
a diarrhoea most serious. The loss of appetite, the more or less 
constant pain, and the absorption of abnormal decomposition 
products, — all these frequently accompany diarrhoeas and in- 
crease their seriousness. 

Constipation. — In constipation the chyme remains in the 
large intestines for an abnormally long time, and more water 
is absorbed from it than usual, with the result that the faeces 
become hard and are passed less frequently than usual. It is 
impossible to draw any sharp line here between what is patho- 
logical and what is physiological. We may say in general, 
however, that infrequent defecation can only be regarded as 
pathological when it gives rise to symptoms. Constipation 
is undoubtedly caused by abnormalities of the large intestines, 
yet it is unprofitable to speculate on the exact nature of these 
abnormalities so long as we do not even know why the normal 
intestines empty themselves so infrequently. 

Causes of Constipation, (a) Improper Food. — In a cer- 
tain proportion of cases the constipation is caused by improper 
food. We have stated that the material in the bowels furnishes 
the normal stimulus to intestinal peristalsis. Every animal 
must take food that furnishes the necessary amount of stimu- 
lus. Thus an herbivora will die of constipation if it be totally 
deprived of the cellulose which normally excites its peristalsis, 



THE DIGESTION 299 

and even carnivorous animals may suffer seriously from con- 
stipation if fed solely on such easily absorbable material as 
milk, eggs, and meat. A certain number of men place them- 
selves on just such a diet. Though their intestines possess a 
normal irritability, the stimulus to peristalsis is lacking and 
they suffer from constipation. If they take foods which stimu- 
late the intestines either by reason of their coarse, indigestible 
character, or by reason of their content of chemical irritants, 
such as the organic acids, then the constipation is cured. A 
lack of water in the chyme may lead to constipation. This 
is probably the cause of the constipation which so frequently 
accompanies dilatation of the stomach, with hypersecretion 
and the vomiting of large quantities of fluid. Profuse sweat- 
ing also frequently leads to constipation, probably because it 
increases the absorption of water from the intestinal contents. 

(b) Lessened Intestinal Irritability. — In other cases of 
constipation the normal irritability of the intestines is reduced 
more or less, and consequently the normal stimuli are not fol- 
lowed by the customary response. This is apparently the cause 
of the constipation which sometimes accompanies chronic 
catarrh and atrophy of the mucous membrane of the large 
intestines. 

(c) Muscular Weakness. — It is evident that no irritation 
will prove of any value when the muscular coat of the intes- 
tine is greatly weakened by muscular paralysis or atrophy. 124 
Such a muscular atrophy may or may not be associated with 
atrophy of the mucous membrane. Peritonitis is frequently 
accompanied by constipation, and even by total paralysis of the 
intestines. The exact relation between the two is not very 
clear, but, in some cases at least, the inflammatory process has 
extended from the peritoneal covering of the bowel into the 
muscularis. 

(d) Nervous Causes. — The pathological significance of 

" Nothnagcl, Ztft. f. klin. Med., vol. iv. 422. 



300 CLINICAL PATHOLOGY 

the ganglia within the intestinal wall and of their nervous 
connections is quite unknown. Degeneration of this nervous 
apparatus has been described in cases of lead poisoning and 
of chronic constipation, 125 yet similar changes have been ob- 
served in other conditions. 126 

Constipation may be associated with diseases of the central 
nervous system, such as neurasthenia, melancholia, and many 
organic changes. The cause of this constipation is not always 
clear. Occasionally it is of the spastic type, which will be 
described below. Possibly in some cases the central structures 
directly inhibit the intestinal movements through the splanch- 
nic nerves, or possibly there is a diminution in the normal 
nervous influences, which tend to increase peristalsis. Both of 
these, however, are pure hypotheses. 

Thus we see that many causes may lead to constipation. 
Improper food, reduced irritability of the intestines, weakness 
of the intestinal musculature, abnormal nervous influences, — 
all may act independently or in combination. Some cases of 
constipation are cured by exercise, although we do not know 
how it is effected. 

The act of defecation is often assisted by the contractions 
of the abdominal muscles, although in the perfectly healthy man 
this is not necessary, and the peristalsis of the large intestines 
suffices to empty them. In most cases of constipation the 
intestinal peristalsis is primarily at fault, and it is rare to 
find the rectum filled with unexpelled fasces. If such be the 
case, however, then either the presence of the faeces in this 
locality fails to produce the normal stimulus to defecation, or 
the abdominal muscles do not furnish the help which may be 
necessary to expel the accumulated material. 

186 Jiirgens, Berl. klin. Wochenschr., 1882, p. 357 ; Maier, Virch. Arch., 
vol. xc. 

126 Sasaki, Virch. Arch., vol. xcvi. p. 287 ; Schleimpflug, Ztft. f. klin. 
Med., vol. ix. pp. 52, 152. 



THE DIGESTION 301 

(e) Spastic Constipation. — Finally, there is a form of 
constipation which is due to a tonic spasm of the smooth 
muscle of the intestines. 127 Such a spasm may be produced 
by the action of lead and by meningitis, and the condition 
may also occur in association with neurasthenia and hypo- 
chondriacal conditions. In spastic constipation, certain por- 
tions of the intestines, especially of the colon, are firmly con- 
tracted, and do not propel the chyme. These contracted 
intestines may sometimes be felt through the abdominal wall 
as round, hard, somewhat sensitive cords. The spasm of the 
intestines often causes colic, and the fseces are often hard and 
of small caliber, which configuration results from the spasm of 
the intestines. The treatment of this form of constipation 
should be directed to the relief of the muscular spasm. 

Effects of Constipation. — The effects of constipation are 
for the most part subjective, and the general nutrition of the 
patient rarely suffers. Defecation is often extremely diffi- 
cult, and the worry about this tends to upset the nervous 
equilibrium of the patient. Immediately after defecation he 
feels brighter and his head feels freer. These sensations are 
partly suggestive, but are certainly not wholly so, although 
their cause has not been satisfactorily explained. 

( Constipation is often associated with an excess of ethereal 
sulphates in the urine, 128 indicating excessive intestinal putre- 
faction, and it is possible that these putrefactive products may 
cause some of the general symptoms of constipation. It is 
interesting to note, however, that fewer bacteria are passed 
in the foeces during constipation than during health. 120 — Ed.) 

Intestinal Obstruction. — The lumen of the intestines may 
be obstructed by causes that lie outside of it and compress or 
kink the tube. A long mesentery and peritoneal adhesions 

1:7 Fleiner, Berl. klin. Wochenschr., 1893, X". 3. 

"* Herter, Lectures on Chem. Path., p. 204. 

120 Strasburger, Ztft. f. klin. Med., vol. xlix., Nos. 5 and 6. 



302 CLINICAL PATHOLOGY 

will favor kinking. On the other hand, the cause of the 
obstruction may be situated within the intestines. Tumors or 
scars of the wall, large gall-stones or fecal stones, or even 
masses of hard faeces may practically occlude the canal. A 
paralysis of a piece of intestine, from whatever cause, will 
produce the same effects as an obstruction, for the chyme col- 
lects and decomposes in this paretic portion, and the compara- 
tively healthy muscle above is frequently unable to force it by. 

Movable intestines may readily slip into openings, formed 
either by outpocketings of the peritoneum or by fibrous bands 
left from earlier inflammations. A hernia is produced by the 
entrance of a viscus, especially of intestines or omentum, into 
a sac of peritoneum that does not contain these structures 
normally. In some instances the sac itself is physiological, as 
is the case with the fossa duodenojejunalis and the lesser 
peritoneal cavity; in others, the sac is pathological, as is the 
case in inguinal and femoral hernias. 

The viscera are usually forced into the sac by an increased 
intra-abdominal pressure, such as may be caused by coughing, 
defecation, or muscular effort. The intestines lying within the 
sac may functionate normally and give rise to no serious 
symptoms. On the other hand, the passage through them may 
become obstructed. The entrance to the hernial sac is usually 
comparatively narrow, and if the pressure upon the veins 
at the mouth of the sac be sufficient to interfere with the 
return flow of blood, then cedema develops, the volume of 
the intestines increases, and their lumen may be closed, usually 
at the narrow neck of the sac. The mechanism that leads 
to the obstruction in such cases is thus easily understood. 
It is often extremely difficult to return the cedematous loop 
of intestines into the abdominal cavity, partly because it is 
not easy to apply a pressure upon them equal to that which 
forced them out, and partly because the intestines have become 
greatly swollen from the cedema. 



THE DIGESTION 303 

No adequate explanation has yet been given for the sudden 
obstruction that sometimes develops in hernias which have 
existed for a long time without producing symptoms. Experi- 
ments on the cadaver have, indeed, demonstrated that when 
the intestinal coils are overfilled it is difficult to empty them, 
for they tend to become kinked, and the mucous membrane 
often slides over the muscularis, so that it lies in folds at the 
neck of the sac. Yet these experiments do not explain why, 
at a particular time, the intestines should become overfilled; 
and, furthermore, the neck of the sac may not be especially 
narrow in these chronic cases. It seems to me that insuffi- 
cient attention has been paid to the possibility that there may 
be a primary paralysis of the muscularis in these cases, which 
would allow the intestinal contents to accumulate at one spot. 
This hypothesis may possibly serve to explain many cases in 
which no mechanical cause can be found for the obstruction. 
The question cannot be finally answered, however, until we 
possess more evidence from clinical and experimental sources. 

If a piece of intestine possesses a long mesentery with a 
short attachment to the posterior abdominal wall, as is the 
case, for example, with the sigmoid flexure, then it is liable 
to become twisted about its pedicle, thus producing the condi- 
tion known as volvulus. The rapid distention with gas, that 
follows the volvulus, interferes with the movements of the 
intestines, and prevents them from untwisting, and the lumen 
of the canal is obliterated at the point of twisting. 

Intestinal obstruction may finally result if a portion of the 
intestines is carried downward toward the anus within the 
portion immediately succeeding it. The cause of such an 
intussusception is somewhat obscure. 130 It cannot be repro- 
duced experimentally by the mere paralysis of an intestinal 
loop. It would rather appear as if one portion of intestines 

130 Nothnagel, Darmkrankhciten ; Nothnagel, Ztft. f. klin. Med., vol. iv. 
p. 555 ; Leubuscher, Virch. Arch., vol. lxxxv. p. 83. 



304 CLINICAL PATHOLOGY 

drew itself over another that was tetanically contracted, and 
that the invagination increased by the successive inclusion of 
freshly contracted portions. A similar process is frequently 
seen in the normal intestine, but the invagination is then neither 
extensive nor permanent. We do not know what interferes 
with a straightening out of the canal in the pathological cases. 
When the imagination has once passed beyond a certain limit 
the circulation of the enclosed intestines is interfered with, 
and oedema follows. 

In all these obstructions the symptoms depend mainly upon 
the degree of stenosis and the rapidity with which it develops. 
If the lumen of the bowel is only partially and gradually 
encroached upon, the intestines lying immediately above the 
obstruction contract more forcibly than usual and their mus- 
cular tissue undergoes hypertrophy. 131 The cause of these 
increased contractions is not very certain. 132 Gases frequently 
collect above an experimental stenosis, and these, by distend- 
ing the walls of the intestines, would increase the peristaltic 
movements. Yet it often happens that no abnormal collection 
of gases can be demonstrated even though the peristalsis is 
increased and the muscle hypertrophied. A moderate stenosis 
may last for months without giving rise to any symptoms 
other than slight constipation whenever the food is not prop- 
erly chosen. 

If the lumen of the bowel is totally occluded, the resulting 
symptoms are entirely different from those of a gradual and 
partial obstruction. A total occlusion may develop acutely, 
or it may come on during the course of a chronic obstruction, 
owing to the inability of the muscle to force material past the 
partial stenosis. In either case the intestinal contents stagnate 
above the point of obstruction. The bacteria then multiply 
rapidly, for their growth is no longer held in check by the 

m Herczel, Ztft. f. klin. Med., vol. xi. p. 221. 
132 Nothnagel, Ztft. f. klin. Med., vol. iv. p. 532. 



THE DIGESTION 305 

onward movement of the chyme. The resulting decomposi- 
tions are of various kinds, depending partly upon the bacteria 
present and partly upon the material subjected to their action. 
When the obstruction affects the lower part of the small intes- 
tines, large quantities of unabsorbed food material are stag- 
nated and putrefaction is very marked; whereas, if the large 
intestines are affected, some time may pass before any abnormal 
decomposition is apparent, because most of the nourishment 
has already been extracted from the chyme. When putrefac- 
tion occurs, all its varied products are formed, and often in 
large amounts. Of these, the aromatic compounds, such as 
indol and phenol, combine in the body with sulphuric acid 
to form the comparatively harmless ethereal sulphates. As 
a result there is often a most marked increase in the quantity of 
indican and of ethereal sulphates of the urine (see p. 289). It 
is possible, however, that some of the poisonous compounds 
resulting from the intestinal decomposition may escape neutral- 
ization, and that they are responsible for many of the general 
symptoms of intestinal obstruction. For example, the com- 
plicating nephritis is possibly of such a toxic origin. 

The most frequent symptom of intestinal obstruction is 
obstinate constipation. Yet in certain forms of obstruction, 
especially in intussusception, there may be diarrhceal dis- 
charges, composed not of faeces, but of inflammatory or secre- 
tory products of the mucous membrane at and below the 
obstruction. 

As a rule, however, the portion of the intestines below the 
obstruction is totally paralyzed, and not even flatus escapes 
through the anus. Gases collect above the obstruction and 
gradually back up in the direction of the stomach. The intes- 
tines which are thus distended contract vigorously, peristaltic 
and tetanic contractions alternating with each other. These 
can be frequently observed through the abdominal wall, espe- 
cially if the obstruction is an old one and the muscularis has 

20 



306 CLINICAL PATHOLOGY 

had time to hypertrophy. These muscular contractions, espe- 
cially the tonic ones, frequently give rise to the most violent 
colic. The patient begins to vomit soon after the obstruction 
sets in. At first, the vomitus consists merely of the gastric 
contents mixed with bile-stained material from the duodenum. 
If the vomiting continues, however, thin, greenish-yellow ma- 
terial, of a fecal odor, may appear. 133 This material un- 
doubtedly comes from the intestines, and is composed in part 
of unabsorbed, decomposed material, and in part of the prod- 
ucts of intestinal secretion. 

The mechanism by which this material reached the stomach 
is not perfectly clear. One's first thought would be that anti- 
peristaltic movements play an important part, for these occur 
in other conditions, 134 and, even though they have not been 
directly observed in intestinal obstruction, no reason exists a 
priori why they should not be present. Yet some deny their 
existence, holding that the material reaches the stomach by a 
sort of overflow from the intestines, which is assisted by the 
normal peristaltic movements. 135 

As the obstruction continues, the patient loses in weight 
and strength rapidly. The period of increased peristalsis is 
later followed by one of paralysis of the intestines. At first 
this cessation of intestinal movements is caused merely by the 
overdistention of the intestines; for it has been shown, ex- 
perimentally, that greatly distended intestines cease to contract, 
but that they will begin to do so again as soon as the tension 
is diminished. In the later stages of obstruction, however, the 
intestinal paralysis is absolute ; and, experimentally at least, no 
movements can be elicited. This entire absence of peristaltic 
movements in intestinal obstruction indicates an exceedingly 

133 See Leichtenstern, Kongr. f. in. Med., 1889, p. 56, etc. 
m Griitzner, Deut. med. Wochenschr., 1894, No. 48; Hernmehr, Arch. 
f. Verdauungskr., vol. viii. p. 59. 

135 See Nothnagel, Darmkrankheiten. 



THE DIGESTION 307 

grave condition, and, if help is not forthcoming, the patient 
dies in collapse. 

Though it is generally agreed that a period of increased 
peristalsis always precedes the period of paralysis in chronic 
obstruction, some consider that this primary period is absent in 
some cases of acute obstruction. Yet it seems to me that a 
primary period of increased peristalsis is present even in these 
cases, but that it is of such short duration that it is often over- 
looked. How quickly the one follows the other depends upon 
the relation which exists between the degree of obstruction 
and the strength of the muscle. The physician who has not 
observed the case from the beginning might be inclined to 
doubt that any period of increased peristalsis has been present. 

Strangulation. — The severity of the symptoms varies 
greatly in different cases of obstruction. In some, the mete- 
orism, fecal vomiting, and collapse do not occur for days, 
whereas in others these symptoms develop within a few 
hours after the obstruction takes place. These variations de- 
pend largely upon the nature of the occlusion. A simple 
closure of the lumen of the intestines is much less dangerous 
than a so-called strangulation, which may accompany any of 
the different forms of intestinal obstruction. 136 In this latter 
condition the blood-supply of the intestines is affected. The 
mesenteric and intestinal veins are pressed upon and occluded, 
the arteries continue to send blood into the intestines, and 
oedema results. These vascular changes, together with injuries 
to the nerves of the peritoneum, are apparently responsible 
for the rapid and alarming symptoms which ensue. The walls 
of the intestines become infiltrated with fluid, and bacterial de- 
composition proceeds with excessive rapidity within the lumen 
of the strangulated gut. The products of this bacterial 

134 Kirstein, Deut. med. Wochcnschr., 1889, No. 49; Reichel, Deut. 
Ztft. f. Cliir., vol. xxxv. p. 495; v. Mikulicz, Thcrapie dcr Gegcnwart, 
1900. 



308 CLINICAL PATHOLOGY 

activity injure the intestinal walls, so that they no longer oppose 
the normal resistance to the gases which are formed. Con- 
sequently the strangulated piece of intestines becomes enor- 
mously distended (local meteorism). The violent peristaltic 
movements produce the most intense pain, and vomiting be- 
comes uncontrollable. Added to these are certain general 
symptoms, such as the general circulatory changes, the col- 
lapse, and the rapid loss of strength. The circulatory dis- 
turbances are caused, in the first place, by reflexes from the 
peritoneum that act upon the heart and vessels, but especially 
by those that influence the splanchnic vascular area. In the 
second place, they are probably produced directly by the toxic 
action of putrefactive products absorbed from the intestines. 

Meteorism. — The intestines of healthy individuals contain 
gases composed in part of swallowed air and in part of those 
which arise from the decomposition of the intestinal con- 
tents by the digestive juices, and especially by bacteria. 
When air is swallowed, the oxygen in it is absorbed quite 
rapidly, so that the small intestines rarely contain this gas. 
The nitrogen, however, remains in the canal for a much longer 
time. Carbon dioxide is set free by the action of acids upon 
the carbonates in pancreatic juice, bile, and succus entericus, 
but it is generated in much larger quantities during carbo- 
hydrate fermentation. The latter also yields hydrogen and 
marsh gas, and the putrefaction of proteids produces small 
quantities of hydrogen sulphide. Of these various gases, the 
carbon dioxide is absorbed by the blood quite readily, whereas 
the nitrogen, methane, and hydrogen are absorbed much more 
slowly. The quantity and quality of the intestinal gases vary 
greatly, even in a healthy man ; for they depend largely upon 
the quality and quantity of the food taken and upon the 
varieties of bacteria that happen to be present. 

These intestinal gases may produce some variation in the 
size of the abdomen, but rarely does great distention result, 



THE DIGESTION 309 

for the normal intestines can to a certain extent dispose of 
the gases they contain, either by absorption or by expulsion 
through the anus; both processes depending largely upon the 
tonus of the smooth muscle. 

In gastro-intestinal diseases much larger quantities of gas 
may be formed, and those produced in greatest abundance are 
usually the very ones which are least easily absorbed, — viz., 
methane and hydrogen. Yet a mere increased production of 
gas does not necessarily cause meteorism either in a healthy 
individual, or even in some patients with intestinal obstruction. 
It would appear that diminished muscular tonus and insuffi- 
cient absorptive capacity are of much greater importance in 
the production of tympanites than is an excessive formation of 
gases. For this reason, meteorism is especially marked in 
peritonitis and acute strangulation. If the intestines once yield 
to the pressure of gas within them, a vicious circle is estab- 
lished, for this very distention embarrasses their circulation, 
and so diminishes their ability to absorb gas. 

Meteorism, therefore, tends to develop whenever a weak- 
ness of the intestinal musculature is associated with an over- 
production of gas within the intestines. The milder forms of 
tympanites are seen in connection with dyspepsias, enteritides, 
and typhoid fever; the more severe in association with peri- 
tonitis and intestinal obstruction. 

The meteorism that is present at times in hysterical patients 
has not been satisfactorily explained, but seems to depend in 
part upon transitory paralyses of the muscle and in part upon 
the swallowing of large amounts of air. Hysterical paralyses 
are common enough in other parts of the body,, and we see no 
reason why they should not occur in the intestines, and the 
fact seems well established that many hysterical individuals 
swallow air in considerable quantities. 

The gases from the intestines may escape into the peri- 
toneal cavity through a perforation, and SO distend it. This 



310 CLINICAL PATHOLOGY 

is usually fatal, on account of the associated infection of the 
peritoneum. 137 Yet even ordinary tympanites may be exceed- 
ingly serious. The diaphragm is forced upward and its move- 
ments are restricted, the capacity of the lungs is reduced, 
and the right ventricle is pressed upon. In many diseases, 
especially in pneumonia, tympanites is a most serious compli- 
cation. 

Abnormal Intestinal Sensations. — These are various. In 
the first place, a distention of the intestines will reduce the 
sensation of fulness in the abdomen, and if the distention be 
marked, dyspnoea may be produced by the high position of 
the diaphragm. 

Colic results from violent contractions of the intestines. It 
has been said that colic is never produced by the normal 
progressive peristaltic movements, but only by tetanic spasms. 
These are liable to occur whenever the stimuli for peristaltic 
movements are especially strong. The most severe forms of 
colic are seen in connection with intestinal obstruction and 
lead poisoning. Less severe is the colic which may accompany 
intestinal catarrh and cholera nostra. The pain of colic has 
been located by some in the muscles, in which case it would be 
analogous to the pain caused by cramps in voluntary muscles. 
By others it has been located in the peritoneum, for we know 
that, like the other serous membranes, the peritoneum is an 
exceedingly sensitive structure and inflammations in it are 
always accompanied by severe pain. On the whole, it seems 
to me more probable that the pain of colic precedes from the 
sensory nerves situated in the muscularis of the intestines. 

Yet other pains are unquestionably to be referred to the 
peritoneum, such as, for example, those which accompany peri- 
toneal adhesions. These adhesions, which, as a rule, follow 
some previous inflammation, often cause the most annoying 
pain, which becomes worse when the bands are dragged 

m Heineke, Arch. f. klin. Med., vol. lxix. p. 429. 



THE DIGESTION 311 

of peritoneal adhesions are of the greatest 
practical importance, for they may harass the patient for years 
after the original disease has passed awa}'. 

Somewhat similar pains are often experienced by nervous 
individuals, and seem to be of a neuralgic nature, for no ana- 
tomical basis can be discovered for them. They will be dis- 
cussed therefore in connection with diseases of the nervous 
system. 

Diseases of the anal orifice are often the source of severe 
pain. Each time that hard faeces pass over the inflamed or 
ulcerated mucosa the most intense agony is experienced. Per- 
haps even more unpleasant is the condition known as tenesmus, 
in which a constant, violent desire to defecate harasses the 
patient. This is especially liable to be present in diseases of 
the rectum. The inflammatory changes of dysentery fre- 
quently cause this constant desire to defecate, but, owing to 
the lack of fecal material in the rectum, nothing except inflam- 
matory products are passed and these with most excruciating 
pain. 

m Riedel, Arch. f. klin. Chir, vol. xlvii. p. 153; Vogel, Deut. Ztft. 
Chir., vol. lxiii. p. 296. 



CHAPTER VII. 

NUTRITION AND METABOLISM. 

The activities of the living cells are associated with chemi- 
cal changes within them, and with an interchange of food and 
waste material with their surroundings. The sum of all these 
processes is termed metabolism. A discussion of nutrition 
and metabolism ought properly to deal with each organ in- 
dividually, for it is obvious that different tissues require 
different food materials and give rise to different waste 
products. Indeed, the various organs are more or less inter- 
dependent upon one another, and one organ, for example, may 
use material that has been elaborated by another, or may trans- 
form waste products derived from another. In our present 
state of knowledge, however, it is impossible to discuss meta- 
bolism from the stand-point of the individual organs, and we 
are obliged to consider the metabolic processes that take place 
in the body as a whole. Our knowledge of these processes is 
derived mainly from examinations of the food ingested and of 
the various waste products eliminated. 

THE QUANTITATIVE VARIATIONS IN THE METABOLISM OF FATS 
AND PROTEIDS. 

In order to maintain the body, it is necessary to supply it 
with water, mineral salts, and organic bodies, which latter 
include the proteids, carbohydrates, and fats. It is not alto- 
gether certain, however, that this enumeration fully expresses 
the needs of the body, for there have been failures to maintain 
animals upon a diet consisting solely of casein, sugar, fat, and 
salts. 1 

The Caloric Needs of the Body. — The food ingested is 

1 Lumin, Ztft. f. physiol. Chem., vol. v. p. 31. 
312 



NUTRITION AND METABOLISM 313 

utilized partly to repair the tissue waste, and partly to furnish 
energy for muscular movements and for bodily heat. For 
these last purposes it is practically immaterial in what form 
the energy is provided, whether it be as carbohydrates, fats, or 
proteids; the essential point being that the quantity of food 
is sufficient. (The energy contained in the various food-stuffs 
is transformed by the body into mechanical work, chemical 
work, and, especially, into heat. Indeed, Rubner has shown 
that almost the entire energy of the food leaves the resting 
body in the form of heat, and that the heat which results from 
combustion in the body is the same as that which would be 
produced were the foods burned outside to the same waste 
products. 

The unit for measuring quantities of heat is the large 
calorie, which represents the amount of heat necessary to raise 
the temperature of a kilogram of water one centigrade de- 
gree. When equal weights of different food-stuffs are burned 
in the body, different quantities of heat are liberated. Thus 
each gram of fat produces about 9.3 calories, each gram of 
carbohydrates about 4.1 calories, and each gram of proteids 
about 4.1 calories. It will be seen from these figures that the 
energy derived from fat is relatively greater than that derived 
from carbohydrates or proteids. Indeed, one' gram of fat 
furnishes about the same energy as does 2.3 grams of either 
of the other two. It is possible, with certain limitations, to 
replace any constituent of the diet by any other, without dis- 
turbing the equilibrium of metabolism, providing due attention 
be paid to the caloric value of each food-stuff. Each gram of 
fat in the food, for example, may be replaced by 2.3 grams of 
carbohydrates, etc. It is furthermore possible to calculate the 
total quantity of energy contained in any particular diet and 
in this manner to estimate whether or not tins diet contains a 
sufficient amount of energy to cover the caloric needs of the 
individual. 



314 CLINICAL PATHOLOGY 

The amount of energy that must be supplied to the body- 
depends primarily upon the activities of the tissues, and it is 
subject to many influences. This amount has been estimated 
empirically from the mean quantity of food taken by different 
individuals. For an adult of average nutrition and size, the 
following have been given as the approximate number of 
calories necessary per kilo of body weight : 2 

Calories. 

Resting in bed 30 to 34 

Quiet, out of bed 34 to 40 

Moderate work 40 to 45 

Hard work 45 to 60 

A small person needs a relatively greater supply of energy 
per kilo of weight; for, as is well known, a small body has 
a relatively large surface, and would consequently lose more 
heat in comparison to its weight. This is one reason why 
children need more food than adults in proportion to their 
weight. On the other hand, stout individuals need relatively 
less food; and instead of the normal thirty- four to forty-five 
calories, they need only about twenty-six to thirty-six calories 
per kilo of body weight. This difference is due to the facts 
that a large body has a relatively small surface ; that the thick 
layer of fat protects these persons from heat losses; that the 
fat itself is practically dead tissue in the body, and does not 
consume energy; and, finally, that stout individuals usually 
take a minimal amount of exercise. — Ed.) 

Not all variations in the caloric needs of different indi- 
viduals are thus easily explained, and there are reasons for 
assuming that the cells of different persons manifest different 
needs for energy. At least, no other satisfactory explanation 
can be given for the fact that certain men seem to require 
very much smaller quantities of proteids and of energy than 
do others. 3 

2 Moritz, Griindzuge der Krankenernahrung, p. 248. 

3 Buys, cit. in Jahresber. f. Tierch., vol. xxiii. p. 491. 



NUTRITION AND METABOLISM 315 

The Proteid Needs of the Body. — The food must furnish 
the body not only with a sufficient amount of energy, but also 
with a certain minimum of proteids, which is utilized in part 
in the repair of the waste within the cells. 

The steps whereby the proteids of the food are prepared 
for use in the body are not yet accurately understood. It was 
formerly believed that these substances were altered very little 
before being used, but more recent work would indicate that 
the proteids, taken as food, undergo extensive cleavage in the 
body, and that the products of such cleavage are again syn- 
thesized into compounds more suitable for use in the cells. 4 
It is known, for example, that unusual proteids, taken by 
mouth, cannot be demonstrated afterwards in the portal or sys- 
temic blood, that life may be maintained even though only a 
single proteid be taken in the food, and that, finally, if two 
different species of animal receive the same food, the proteids 
of their bodies still remain distinguishable (see p. 171). On 
the other hand, no success has attended the efforts to maintain 
a nitrogenous equilibrium by replacing the proteids of the food 
with cleavage products of a simpler composition than are the 
albumoses and peptones. It would appear from this as if the 
body is unable to build up the proteid molecule unless certain 
substances, not at present known to us, are furnished to it. or 
that it can utilize the products of proteid cleavage only when 
they are supplied in the nascent condition. It is possible, how- 
ever, that the cleavage products have never yet been given in 
proper proportions, and that we shall yet be able to maintain 
life without using proteids. 5 

The mimimal amount of proteid, necessary for the needs 
of the body varies with the condition of proteid nutrition that 
is to be maintained and with the work which the body per- 

4 Loewi, Arch. f. cxp. Path., vol. xlviii. p. 303; Cohnheim, Ztft. f. phys. 
Chcm., vol. xxxiii. p. 9. 
' Leowi, loc. cit. 



316 CLINICAL PATHOLOGY 

forms. 6 Although the quantity given by Voit seems consider- 
able (one hundred and eighteen grams of proteid for a man 
of seventy kilograms), and although less is sufficient for an 
individual when he is at rest or when other forms of food 
are taken in great abundance, 7 nevertheless there is a growing 
inclination to regard these older figures as approximately cor- 
rect for a healthy individual, and to believe that the capabilities 
of the body are liable to be diminished if less than this amount 
of proteid food be taken. On the other hand, as Rubner has 
shown, proteids in the food should not exceed a certain maxi- 
mum proportion, for if they do, an excessive amount of heat 
is liberated immediately after meals, and this is not only use- 
less but may be directly harmful if the heat regulation in the 
body be imperfect (see p. 322). 

In what way the cells are supplied with proteids is not 
known, though it would seem probable that they derive them 
from the blood plasma. This supposition is supported by the 
results of precipitin experiments, for these have shown that 
the proteids of the plasma and of the cells of an animal are 
apparently more closely related than are the proteids from the 
same organs of different species of animals. 

We do not know what regulates the needs of the cells for 
proteids, though many facts would seem to indicate that only 
a small part of the minimum proteids necessary for the body 
actually becomes living protoplasm. It is possible that the 
excess is necessary for the reason that only a certain portion 
of the proteid molecules of the food can be utilized in building 
up living tissue. 

Inanition.— Inanition may be due to a variety of causes. 
Of these, the most important are, first, an insufficient inges- 

6 Erwin Voit and Korkunoff, Ztft. f . Biol., vol. xxxii. p. 58 ; J. Munk, 
Du Bois' Arch., 1896, p. 183; Rubner, Energieverbrauch. 

'See v. Noorden, Path. d. Stoffwech., p. 114; Rubner, Ztft. f. Biol., 
vol. xix. p. 313. 



NUTRITION AND METABOLISM 317 

tion of food, either from lack of food or lack of appetite, and 
secondly, an insufficient absorption of material from the gastro- 
intestinal canal. Practically, inanition is most frequently seen 
in connection with diseases of the digestive system. 

It is necessary to distinguish an insufficient supply of food 
as a whole, a caloric insufficiency, from an insufficient supply 
of proteid material, a proteid insufficiency. These two are 
more or less independent of each other, and it is possible, for 
example, that a patient should gain in weight and yet suffer 
from an insufficiency of proteids. 

If too little food be supplied to the body, then the individual 
must live upon his own tissues. His glycogen and fats can 
furnish him with energy. In addition to this, however, he 
consumes a certain minimal quantity of proteids, which are 
derived from the less important organs of his body. The 
amount of proteids thus consumed depends partly upon the 
quantity of fat and glycogen at his disposal and partly upon 
individual peculiarities. During the first few days of an 
absolute fast the excretion of nitrogen is influenced by the 
quantity of proteids that had been taken just before the fast 
began. As soon as this excess of nitrogen has been elimi- 
nated, however, the quantity in the urine sinks to a minimum 
and remains there for a few days. Later it again increases 
possibly because all of the glycogen in the body has been 
used up. 8 

During the earlier stages of starvation, therefore, the 
energy necessary for muscular movements and for heat, is 
supplied by the combustion of the glycogen and fats stored 
up in the body. The more valuable proteid material is thus 
protected from consumption. When the store of non-nitro- 
genous material comes to an end, however, the proteids them- 
selves must be utilized to supply the necessary energy to the 

8 May, Ztft. f. Biol., vol. xxx. p. 29 ; Lehmann, Midler, Munk, Senator, 
Zuntz, Virch. Arch., vol. exxxi. Supplement. 



318 CLINICAL PATHOLOGY 

body. 9 The living tissues then break down rapidly; yet a 
certain discrimination still takes place. The more important 
organs live at the expense of the less important ones, and 
Voit has shown that the former will retain their normal weight 
practically unaltered up to the end. The greatest loss is sus- 
tained by the muscles and fatty tissues; then follow the skin, 
the liver, and the bones ; whereas the heart and central nervous 
system are spared to the very last. 10 

(During acute starvation the elimination of chlorides in the 
urine is markedly diminished and may reach one tenth or less 
of the normal amount. This is due to the tendency on the 
part of the kidneys to maintain a constant quantity of chlo- 
rides in the body; and when none are taken in the food, the 
small amount eliminated corresponds approximately to that 
derived from the breaking down of the tissues. In the later 
stages of starvation the excretion of calcium and magnesium 
salts, as well as of the phosphates, is increased; probably be- 
cause there is a pathological breaking down of the osseous 
tissues. — Ed.) 

Absolute starvation is rarely seen by the physician, but 
partial inanition is by no means infrequent, and its treatment 
furnishes one of the most important problems that confront the 
practitioner. Usually, in these cases, both the total caloric 
energy and the proteids in the diet are insufficient. The 
amount of this deficiency may vary up to absolute starvation. 

The effects of starvation upon the individual depend, in 
the first place, upon how complete it is. If the body consumes 
thirty-five calories per kilo a day and if it receives only ten 
from the food, then it must supply twenty-five calories from 
its own substance, and the condition is naturally a much more 

8 E. Voit, Ztft. f. Biol., vol. xli. p. 550; Schulz, Pfluger's Arch., vol. 
lxxvi. p. 379; ibid, Munch, med. Wochens., 1899, No. 16. 

10 C. Voit, Physiologie d. Stoffwechsels., p. 95; Sedmayer, Ztft. f. 
Biol., vol. xxxvii. p. 35. 



NUTRITION AND METABOLISM 319 

serious one than if it had received thirty calories in the food 
and had supplied only five from its own substance. Further- 
more, starvation is withstood much better if the patient be 
stout, for he then has a larger amount of fat that can be utilized 
to supply energy. This serves to postpone the time at which 
the non-nitrogenous stores in the body give out, and the living 
tissue itself must be consumed to supply energy. Finally, the 
course of inanition is influenced by the demands made upon 
the energy within the body, and the condition is a more serious 
one when the individual must work or when he is not well 
protected by clothing, etc., from losses of heat. 

In certain diseases, hunger and insufficient nourishment are 
often surprisingly well borne; better, indeed, than they are 
in health, for the body then seems to be able to limit its con- 
sumption of proteids and energy. Astonishingly low figures 
have been found in such cases, and patients have often gained 
in weight on a diet that would be entirely insufficient for a 
healthy man. 11 The amount of heat produced in the body 
during a short fast is about the same as that produced when 
the individual is consuming moderate amounts of food. If, 
however, the patient suffers from prolonged partial starvation, 
then the amount of heat produced in the body seems to be 
lessened, and one gets the impression that the ability to limit 
the expenditure of energy is quite characteristic of wasting- 
diseases, such as diabetes, for example. 

The Effects of an Oversupply of Food. — It is necessary to 
discuss the effects of increasing the nitrogenous and the non- 
nitrogenous elements in the food separately, for the laws gov- 
erning each are different. We may say, in a general sort of 
way, that the cells of the body ordinarily decompose all the 
proteids taken in the food. When proteids are taken in 

11 F. Miiller, Ztft. f. klin. Med., vol. xvi. p. 496; Nebelthau, Ztrbl. f. 
in. Med., 1897, p. 977; G. Klemperer, Ztft. f. klin. Med., vol. xvi. p. 550; 
Richtcr, Arch. f. exp. Path., vol. xliv. p. 239. 



320 CLINICAL PATHOLOGY 

abundance, and the total caloric energy of the food is not too 
greatly increased, there is merely a slight retention of nitro- 
genous material during the first few days of the new diet. 
Very soon, however, the body reaches a condition in which it 
is consuming all the proteids furnished to it, and it is then 
said to be in nitrogenous equilibrium. 

If the tissues happen to be in need of new material, as is 
the case during growth and convalescence, then it is possible 
that a considerable proportion of the extra supply of proteids 
may be retained in the body and may be built up into living 
tissue. 

It is even possible to cause a considerable retention of 
nitrogenous material in the bodies of normal animals by feed- 
ing them with large quantities of both nitrogenous and non- 
nitrogenous food. 12 Apparently the same result may be 
attained even more easily in man. 13 We do not know cer- 
tainly whether this nitrogenous material is retained in the 
body as proteids or as other compounds. It is interesting to 
note in this connection that when growing children or con- 
valescents retain nitrogenous material in their bodies, they 
are taking a diet that contains an excessive amount of energy. 14 

The mere ingestion of fats or carbohydrates in great ex- 
cess tends to diminish the excretion of nitrogen in the urine; 
or, in other words, it tends to cause a retention of nitro- 
genous material in the body. This fact has been variously 
interpreted. E. Voit considers that the cells utilize those foods 
which are supplied to them in greatest abundance; whereas 
Pfliiger and others believe that the selection of material for 
consumption is a property of the living protoplasm, and as 

12 Pfliiger, Pfliiger's Arch., vol. lxxvii. p. 424. 

"Liithje, Ztft. f. klin. Med., vol. xliv. p. 22; Kaufmann and Mohr, 
Berl. klin. Wochens., 1903, No. 8; Kaufmann, Ztft. f. diat. Ther., vol. vii., 
Nos. 7 and 8. 

14 Camerer, Ztft. f. Biol., vol. xxxiii. p. 320 ; Heubner, Ztft. f . diat. 
Ther., vol. v. p. 1 ; Svenson, Ztft. f. klin. Med., vol. xliii. p. 86. 



NUTRITION AND METABOLISM 321 

such is almost independent of which foods are supplied in 
excess. We cannot enter into a discussion of this physiological 
problem, but may state our belief that the growth of living 
tissue depends primarily upon the activities of the cells. In 
virtue of some unknown property these latter grow and mul- 
tiply, and their growth and multiplication are especially excited 
by functional activity; providing, of course, that a supply of 
building material is at hand. When the physician wishes to 
increase the living protoplasm of the body, therefore, he 
should remember that it is more important to increase the 
functional activities of the cells than to furnish the body with 
an oversupply of food. 

In the metabolic cleavage of proteids certain non-nitro- 
genous compounds are split off, related in all probability to 
the carbohydrates. The laws, governing the consumption of 
these, are the same as those governing the consumption of 
other non-nitrogenous substances. 

We have seen that the amount of energy needed by the 
body depends primarily upon the work performed and the 
heat expended. A person lying in a warm bed, for example, 
expends less energy than does one who works hard eight or 
ten hours each day, or who is exposed to very cold weather. 
When excessive quantities of non-nitrogenous food are taken 
in the diet, the excess is not burned up, as are proteids, but it 
is stored in the body, as glycogen or as fat. A discussion of 
the storage of glycogen will be postponed until we consider 
the subjects of diabetes and of fever. In regard to the storage 
of fats, it must be remembered that this is largely independent 
of the nitrogenous metabolism, and that it is possible for the 
body to lose nitrogen and at the same time to gain fat, and 
that it is even possible for death to occur from lack of proteids 
at a time when the fat of the body is well preserved. 

(Rubner 18 has shown that if dogs he kept at a uniform 

"Die Gesetze des Energievcrbruudis bei der Ernahrung, 1902. 

21 



322 CLINICAL PATHOLOGY 

temperature of 33 ° C, the ingestion of any food is followed 
by an increased production of heat in their bodies. The 
amount of this excessive quantity of heat varies according 
to the character of the food. When proteids are taken, about 
thirty per cent, of the energy contained in them was immedi- 
ately given off as extra heat; when fats were taken, about 
twelve per cent, was thus eliminated ; and when carbohydrates 
were taken, about six per cent. This specific action of different 
foods remains the same whether small, medium, or large 
quantities are ingested. If the animals were exposed to a low 
temperature, the extra heat thus produced was utilized to keep 
their bodies warm, thereby avoiding the necessity of increas- 
ing the ordinary production of heat in the muscles. At a 
temperature of 33 ° C, however, the extra heat was eliminated 
without apparently serving any useful purpose. 

It seems improbable that the increased production of heat 
which follows the ingestion of proteids could be caused by 
the increased activities of the digestive glands; for meat 
extracts stimulate these glands, and yet do not increase the 
heat production in the body. Rubner believes that this exces- 
sive heat is caused by a cleavage of the proteid molecules into 
their nitrogenous and non-nitrogenous constituents. He sup- 
ports this view with observations on the effect of artificially 
increasing the proteid metabolism by the administration of 
phloridzin, and he shows that the heat so produced was ap- 
proximately the same as when proteids were taken by the 
mouth. — Ed. ) 

Disturbances in Fat Metabolism. — We have said that, if 
large quantities of non-nitrogenous material are taken in the 
food, the unused excess is stored up in the body either as 
glycogen or as fat. The quantity of fat in the body depends, 
therefore, to a great extent upon the relation that exists 
between the supply of, and the demand for, energy-producing, 
material. 



NUTRITION AND METABOLISM 323 

Different classes of food-stuffs produce different effects as 
regards the tendency to accumulate fat. For example, when 
proteids are eaten, the general metabolism is accelerated far 
more than when fats or carbohydrates are taken, and conse- 
quently less energy is left for storage. Whether fat is ever 
formed directly from proteids or not, need not be discussed 
here, for very little, if any, is derived from this source. In 
either case, an excess of proteid material in the food would 
favor a retention of fat in the body, for the reason that the 
non-nitrogenous products of proteid cleavage may be utilized 
for energy. This would spare the fats and carbohydrates, 
and allow them to be stored. 

The carbohydrates of the diet that are not burned im- 
mediately are deposited in the body partly as glycogen and 
partly as fat. 16 That carbohydrates may give rise to fat in the 
body has been demonstrated any number of times. Apparently 
this transformation takes place with the elimination of carbon 
dioxide, for the respiratory quotient may rise to as high a 
figure as 1.3 during this formation of fat from carbohydrates. 17 
The fat that is thus formed is rich in stearin and palmitin, but 
poor in olein. 18 In what part of the body the transformation 
takes place is not known, though there is some evidence that 
it occurs in the liver. 

If fat is ingested in excessive quantities, it is deposited 
as such in the body. The composition of animal fat is there- 
fore, to a certain degree, dependent upon the composition of 
the fats taken by the mouth. 19 In spite of this fact, however, 
the body fat in man and in many animals preserves a fairly 
constant composition. This may be explained on the assump- 

16 For the literature and discussion of this subject, see Rosenfeld in 
Asher-Spiro, Ergcbnisse der Physiol., vol. i. p. 345 ; vol. ii. p. 50. 

17 Bleibtreu, Pfliiger's Arch., vol. lxxxv. p. 651. 
" Rosenfeld, loc. cit. 

"• Ibid., p. 673. 



321 CLINICAL PATHOLOGY 

tion that the body tends to pick certain fats out of the food 
for storage, or that the food commonly taken is really of a 
more constant composition than is ordinarily believed. 

The relation of the ingestion of fluids to fat metabolism 
is a much-discussed and still unsettled subject. Many stout 
individuals drink a considerable quantity of liquids, especially 
of beer, and it often happens that when the latter is stricken 
from the diet, a loss of weight promptly follows. This result 
is due in part to the loss of energy that would be derived 
from the alcohol and carbohydrates of the beer ; but it may be 
due in part to the lessened quantity of fluids taken. Small 
amounts of other drinks, such as coffee, tea, bouillon, or light 
wine, are often taken to increase the appetite, and if these be 
omitted the individual may eat less and so lose weight from 
this cause. Although these facts are of the greatest practical 
importance, they have no theoretical bearing on the question 
as to whether or not fluids directly influence the storage or 
decomposition of fats in the body. Though this question has 
not yet been satisfactorily settled, 20 it seems worth while to 
review some of the evidence bearing upon it and call attention 
to some of the difficulties encountered in its solution. 

It is a surprising fact that while animals are being fattened, 
very little water is usually allowed them ; 21 from which we 
may infer that a relatively dry diet certainly does not seriously 
interfere with the accumulation of fat in the body. 

The question as to the effect of liquids upon the accumula- 
tion of fat in man is a difficult one to solve; for in him the 
only method whereby we can practically estimate a gain or loss 
of fat is weighing, and a difference in weight might be equally 
well caused by a change in the quantity of proteids, of gly- 

20 Oertel, Allge. Ther. d. Kreislaufstor., 1891, p. 147 ; Lorenzen, Diss. 
Erlangen, 1887. 

21 Hennenberg, Kongr. f. in. Med., 1885, p. 46 ; Vogel, Jour. f. Land- 
wirtsch., vol. xxxix. p. 37. 






NUTRITION AND METABOLISM 325 

cogen, or of water in the body. The first two of these may- 
be neglected practically, for the variations that they undergo 
are not great. The third, however, is of the utmost importance 
in a consideration of this question, and it constitutes a con- 
siderable source of error whenever we assume that a gain or 
loss of weight is necessarily caused by a correspondingly great 
gain or loss of body fat. 

Stout persons ordinarily drink large quantities of water, 
probably because they perspire so freely, and this water is 
not all immediately excreted, but some is stored in the body. 
If, now, the patient refrains from drinking water, and takes 
much exercise, he loses weight rapidly. The main cause of 
this early loss of weight, however, is the loss of water. There 
simply results a drying-out of the body. 22 Indirectly this loss 
of water may assist in reducing the fat in the body, for when 
the weight of a stout person is lessened by the loss of fluids, it 
is possible that he will take more exercise and so consume 
more fat. 

It will be seen from these considerations that different 
factors render this question a most difficult one to solve. At 
present we possess no conclusive evidence that the limitation 
of fluids directly influences fat metabolism; though such a 
limitation may indirectly reduce the weight of the body either 
by removing water from it, by diminishing the amount of food 
taken, or by increasing the ability to take exercise. 

Pathological Accumulations of Fat. — No sharp distinc- 
tion can be made between pathological and physiological 
accumulations of fat, and it is often a matter of opinion as to 
whether a given person is too stout or not. The line sepa- 
rating the normal from the abnormal should be drawn at the 
point where the general health and the capabilities of the 
individual begin to be impaired. When these latter are 

"Dennig, Ztft. f. phys. Then, vol. i. p. -'Si : Zuntz, Ther. d. Gegenw., 
1901, July. 



326 CLINICAL PATHOLOGY 

affected, we are justified in speaking of a pathological accumu- 
lation of fat. 

Fat tends to collect in certain parts of the body, especially 
in the subcutaneous tissues and the mesentery, and about the 
heart, the kidneys, and the liver. In young animals it may 
also collect in the muscles between the individual muscle- 
fibres, 23 whereas in older animals it tends to collect in the 
above-mentioned situations. 

The individual who suffers from excessive accumulations 
of fat gradually becomes less and less able to work. This is 
due, in part, to the increased weight of the body, for more 
exertion is required to execute the same movements. On 
this account, fat persons are inclined to avoid all unnecessary 
exertion. If they do so, their muscles tend to atrophy from 
disuse, and a vicious circle is thus established. The patient 
avoids movements because his body is too heavy, and the lack 
of exercise weakens his muscles so that he is less able to move. 
Most stout people also perspire very readily, because their 
thick layer of fat diminishes the amount of heat given off 
from the surface of the body by radiation and conduction. 
This sweating is very unpleasant, and furnishes another excuse 
for their avoiding exercise. 

In Rubner's laboratory the capabilities of lean and stout 
men have been carefully studied under different conditions of 
temperature and humidity, 24 and it has been shown that, as 
the temperature and humidity of the air increases, the ability 
of stout people to work diminishes rapidly, for they quickly 
become overheated, and perspire profusely. Their fat thus 
renders them less able to work, and soon causes unpleasant 
subjective sensations from overheating. 

Finally, very stout people avoid exertion because they get 

23 F. Muller, Path. d. Stoffwechsel., p. 204. 

24 Schattenfroh, Arch. f. Hyg., vol. xxxviii. p. 93 ; Wolpert, ibid., vol. 
xxxix. p. 298; Rubner, Beitrage z. Ernah. im. Knabenalter, Berlin, 1902. 



NUTRITION AND METABOLISM 327 

out of breath so easily. Their dyspnoea is due, in the first 
place, to the increase in abdominal fat, which limits the move- 
ments of the diaphragm ; in the second place, it is due to the 
additional weight of the body, which necessitates more actual 
work for the accomplishment of the same movements; in the 
third place, it is due to a weakness of the muscles or to an 
associated anaemia; and finally it is due to the cardiac disturb- 
ances, which are so often present in obese individuals and 
which have already been described (p. 68) . It is thus apparent 
that excessively fat persons suffer in a variety of ways, partly 
on account of the presence of the fat itself and partly on 
account of the weakness of the general or cardiac musculature. 

The primary cause of obesity lies in a misproportion be- 
tween the energy taken in the food and the amount expended 
by the body. As we have just said, stout people usually 
show a disinclination to exercise, and this, by diminishing the 
expenditure of energy, favors the deposition of new fat in 
the body. Furthermore, many stout persons eat to excess, 
and the carbohydrates and fats that they eat are especially 
disadvantageous. In certain instances the absorption of pro- 
teids seems to be diminished, and the patient suffers, at one 
and the same time, from too much fat and too little proteid. 25 
Alcoholic beverages certainly tend to increase obesity. In the 
first place, they furnish a not considerable amount of energy 
in the form of alcohol, and frequently also in the form of 
carbohydrates (beer) ; and, in the second place, they tend to 
take away the energies of the individual, and so to diminish 
the exercise that he takes. 

These causes, singly or together, are responsible for most 
cases of obesity. It is merely a problem in arithmetic. A 
certain amount of energy is taken in the form of food, a 
certain amount is lost as heat and work, and the remainder is 
stored up in the body, mainly as fat. As soon as the accumu- 
"Rubner, Beitr., etc. 



328 CLINICAL PATHOLOGY 

lation of fat begins to deter the patient from taking- active 
exercise, a vicious circle is established, and he tends to increase 
in weight more and more. 

The question has been raised as to whether all cases of 
obesity can be explained in this comparatively simple manner. 
Physicians certainly have the impression that not all cases are 
due to a simple misproportion between the energy taken in 
and that given out, and it seems as if many persons, in spite 
of abundant nourishment and little exercise, remain lean, 
whereas others become stout, even though they eat but little 
and do considerable work. 

It is extremely difficult to form a judgment on this ques- 
tion. In the first place, it often happens that, although the 
patient thinks he is not eating to excess, he is really doing so. 
Then we have no accurate method for determining the amount 
of exercise that he takes. There are the most extraordinary 
individual variations in this respect, as can be readily im- 
agined if we compare a nervous individual, constantly in 
motion and all his muscles tense, with a phlegmatic person, 
who never executes an unnecessary movement. The energy 
expended by each is vastly different, even while they are 
accomplishing the same task. Finally, factors that influence 
heat losses must be considered; such as, for example, the 
thickness of the clothing, the temperature of the surrounding 
air, its moisture, etc. All these influence, to some degree, the 
consumption of energy in the body. 

Yet, even allowing for all of them, there still remains the 
impression that some men exhibit an unusual relationship be- 
tween the diet, the exercise taken, and the fat deposited. Some 
children, for example, show a remarkable tendency to become 
stout; or certain families are known for the obesity of their 
members; some anaemic persons tend to accumulate fat, etc. 
To be sure, it may be answered that, when the parent eats to 
excess, the children learn the same habit ; or that the anaemias 



NUTRITION AND METABOLISM 329 

tend to limit the amount of exercise taken, etc. Nevertheless, 
the impression remains that, for some unknown cause, certain 
individuals possess a peculiar tendency to lay on fat. 

We should not, however, trust to impressions. The ques- 
tion is one that can only be solved by careful and exact experi- 
ments, and up to the present these have furnished no evidence 
which would indicate that such a constitutional tendency to 
obesity, in the sense of a slower rate of metabolism, actually 
exists. For example, Rubner has shown that, of two brothers, 
one stout and the other thin, the former burned up even 
more fat than the latter. Others have demonstrated that stout 
persons consume a normal amount of oxygen and give off a 
normal amount of carbonic acid gas during fasting; and, 
although the increase in heat production that immediately 
follows the taking of food is said to be less in stout than in 
thin persons, 20 we are hardly justified from this fact alone in 
assuming a slower rate of metabolism in the former. 

The gain in weight that so often follows castration has 
been cited as an example of a constitutional change leading 
to obesity. It is certain that many, though not all, castrated 
animals and men gain in weight. We may question, how- 
ever, whether this gain is directly due to the loss of a hypo- 
thetical accelerating influence of the genital organs upon 
metabolism, or whether the gain is not indirectly due to 
changes in the temperament of the individual, in his appetite 
for food, his desire to exercise, etc. Liithje, 27 has made a 
careful comparative study of the nitrogenous metabolism, and 
a partial study of the carbon and mineral metabolisms of cas- 
trated and normal dogs over a period of more than a year, 
and, finally, at the end of this time, he has determined the 
total composition of their bodies. No differences could be 
found between the normal and pathological animals, and we 

"Jaquct and Svenson, Ztft. f. klin. Med., vol. xli, p. 376. 
"Arch. f. exp. Path., vol. xlviii. p. 184; vol. 1. p. 268. 



330 CLINICAL PATHOLOGY 

must conclude from these experiments that castration does not 
directly affect the body metabolism. Although other observers 
have found certain differences by other methods, 28 neverthe- 
less it seems to me that Liithje's experiments are the most 
conclusive we have. 

This much is certain, that obesity results from a failure 
to consume all of the nourishment taken. It is possible that 
a lessened rate of cellular metabolism plays an important part 
in certain cases, though personally I do not believe that this 
has yet been proved. 

The association of obesity with anaemia, with gout, with 
arteriosclerosis, and with various forms of calculi should here 
be mentioned, though the exact causal relation between these 
is unknown to us. 

Pathological Changes in the Metabolism of Proteids 

As has been described, the growing child and the convalescent 
from infectious diseases are alike able to retain some of the 
nitrogen taken in the food; whereas a normal individual 
under like circumstances would soon come into a condition 
of nitrogenous equilibrium. Even in the above instances, 
however, a great excess of food is usually taken. 

Pathological Destruction of Proteid Material. — If, as has 
been said, the ingestion of proteids falls below a certain limit, 
or if the body has no non-nitrogenous material at its dis- 
posal and is not oversupplied with proteids in the food, then 
the living nitrogenous substances in the tissues must be con- 
sumed to supply the body needs. In the class of cases which 
we now wish to consider, however, there is a pathological 
consumption of the body substance, and especially of its pro- 
teids, even though an ordinary amount of food be taken. If 
such a patient fasts, his excretion of nitrogen is considerably 

28 Loewy and Richter, Engelmann's Arch., 1899, Supplement ; ibid., 
Berl. klin. Wochens., 1899, No. 50; Ztrbl. f. Physiol., 1902, No. 17; Loewy, 
Ztrbl. Physiol., 1902, No. 50. 



NUTRITION AND METABOLISM 331 

greater than is that of a normal individual of like weight, etc. 
If an attempt be made to bring him into a condition of nitro- 
genous equilibrium, this is often a complete failure, for, as 
proteids are added to his diet, the consumption of nitrogenous 
material also increases, so that the output of nitrogen remains 
constantly somewhat greater than the intake. In certain of 
these cases, however, it is possible to maintain a nitrogenous 
equilibrium by using enormous quantities of food. 

A pathological proteid destruction of this character takes 
place in all forms of fever, and it will be referred to again in 
that connection. It also occurs in many patients with car- 
cinomata and other malignant tumors, 29 in many with tuber- 
culosis, even though no fever is present, in severe anaemias, 30 
and in certain intoxications, as from phosphorus. 31 Possibly, 
also, it is present in other conditions, such as scleroderma, 
lichen ruber, and pemphigus vegetans. 32 

In the conditions enumerated, excessive quantities of fat 
are also frequently consumed, for the diet is often an insuffi- 
cient one, but this consumption follows the ordinary physio- 
logical laws of inanition; whereas the destruction of proteids 
is of a pathological character. Which cells of the body suffer 
most from this consumption of proteids has never been de- 
termined, though one would be inclined to believe that the 
loss falls upon the same organs as it does in inanition (see 
p. 318). 

Not all patients with carcinomata, severe anaemias, or 
tuberculosis suffer from this increased destruction of proteids, 
and it would appear, therefore, that other causative factors 
are operative in these cases. In view of the fact that certain 

20 F. Miiller, Ztft. f. klin. Med., vol. xvi. p. 496; Kongr. f. in. Med., 
1889, p. 396; G. Klemperer, Ztft. f. klin. Med., vol. xvi. p. 550. 
10 Rosenquist, Ztft. f. klin. Med., vol. xlix. p. 193. 
" Fraenkel and Rohmann, Ztft. f. phys. Chem., vol. iv. p. 439. 
" Stiive, Arch. f. Derm. ti. Syph., vol. xxxvi. p. 51. 



332 CLINICAL PATHOLOGY 

poisons, such as phosphorus, may accelerate the destruction 
of proteid material, F. Miiller has advanced the hypothesis 
that toxic substances are also responsible for the increased 
proteid destruction that accompanies certain cases of carci- 
noma. These toxic substances have never been isolated, yet 
there is every reason to believe that this explanation is a 
correct one. Only when this hypothetical poison is produced, 
does the disease lead to a destruction of proteid material. 
This theory is supported by the fact that in tuberculosis and 
carcinoma we sometimes see toxic symptoms resembling those 
of diabetic coma. 

A pathologically increased nitrogenous metabolism is a 
most serious condition, for it becomes impossible to maintain 
the patient's nutrition, and the loss of proteids may eventually 
prove fatal. 

The Metabolism in Exophthalmic Goitre. — Many patients 
suffering from this disease manifest no peculiarities as regards 
their metabolism; others, however, show periods of fair to 
good nutrition alternating with periods of emaciation. This 
emaciation may occur even when the appetite is considerably 
increased. One of F. Muller's 33 patients, for example, weigh- 
ing only twenty-nine kilos (sixty-four pounds,), lost both in 
nitrogen and general weight, even though the diet furnished as 
much as sixty-eight grams of proteids per day and fifty-eight 
calories for each kilo of body weight. In such cases a patho- 
logical consumption of both nitrogenous and non-nitrogenous 
material is undoubtedly taking place in the body. As a rule, 
it is possible to attain a nitrogenous and caloric equilibrium 
in these patients by giving them very large quantities of food. 34 

It is very interesting that, in Matthes's cases, the excessive 
consumption of proteid material disappeared after the re- 

23 Arch. f. klin. Med., vol. li. p. 401. 

24 Scholtz, Ztrbl. f. in. Med., 1895, Nos. 43 and 44 ; Matthes, Kongr. f. 
in. Med., 1897, p. 232. 



NUTRITION AND METABOLISM 333 

moval of a large part of the thyroid gland, thus conclusively 
demonstrating that the pathological thyroid function increased 
the consumption of nitrogenous and non-nitrogenous material 
in the body. Indeed, it was found that if thyroid gland were 
administered to these patients after their operations, the excre- 
tion of nitrogen rose to what it had been previously. 

The amounts of oxygen absorbed and of carbon dioxide 
eliminated by patients with exophthalmic goitre are greater 
than the normal. 33 After the removal of the thyroid gland 
from rabbits, these animals show an abnormally low " respira- 
tory interchange of gases" when fasting, and if thyroid sub- 
stance be then administered to them, this interchange returns 
to the normal. 36 We see, therefore, that in certain patients 
with exophthalmic goitre there is an increased consumption 
not only of proteids but also of non-nitrogenous materials. 
In this last feature the metabolism differs from the increased 
proteid metabolism of carcinoma, and it is even possible that 
the loss of proteids in exophthalmic goitre is merely secondary 
to the loss of non-nitrogenous material. 37 

The administration of the thyroid gland to healthy men 
or animals, either by way of the digestive tract or by subcu- 
taneous injections, increases the bodily consumption of pro- 
teids and fats. 38 In a certain proportion of cases this loss 
may be covered by an abundant diet. Here again it is un- 
certain whether the destruction of proteids is secondary to the 
destruction of fats or not, 30 and Scholtz, 40 for example, found 
that when thyroid substance was given to cretins, the fat was 
consumed and that the proteids were not affected. 

35 Magnus-Levy, Berl. klin. Wochens., 1895, No. 30. 
*° Maier, Diss. Wiirzburg, 1900. 
37 F. Miiller, Kongr. f. in. Med., 1897, p. 239. 

88 Schondorff, Pfliigcr's Arch., vol. lxvii. p. 395; Voit, Ztft. f. Biol., 
vol. xxxv. p. 116. 

39 Schondorf and Voit, loc. cit. 

40 Kongr. f. in. Med., 1902, p. 475. 



334 CLINICAL PATHOLOGY 

A lack of thyroid function affects the body in still other 
ways. 41 Thus, if the thyroid and parathyroids are removed 
from an animal, tremors and peculiar convulsions often de- 
velop, which resemble tetany, and yet are not identical with 
it, 42 and fever may also be present at times in these animals. 
The convulsions sometimes involve the respiratory muscles and 
so cause death. 

If the function of the thyroid glands be gradually dimin- 
ished, or if, after total extirpation, the more acute symptoms 
are eliminated by the administration of thyroid substance, then 
nutritional disturbances may develop in the skin, nails, bones, 
and other organs. The skin becomes thick and immobile 
owing to a collection of a mucin-like material in the corium, 
the connective tissue fibrils thicken, and the hair falls out. 
Weakness of the muscles and disturbances of sensation are 
associated with a general loss of intelligence; and if the 
gland be removed from growing animals, the growth may be 
stunted. 

These symptoms closely resemble those of myxcedema and 
cretinism, in which diseases the thyroid gland is found to be 
diseased or absent. The variations in symptoms seen in these 
diseases are probably due to the varying intensity and character 
of the thyroid lesion, as well as to the age of the patient when 
the disease began. The changes in myxcedema and cretinism 
are to be attributed, therefore, to an insufficient function on 
the part of the thyroid gland. As proof of this we have the 
remarkable results obtained by the administation of thyroid 
substance to these patients. 43 

Exophthalmic goitre, on the other hand, is probably due 
to an increased thyroid function. In favor of this view are 
the facts that a partial extirpation of the thyroid has improved 

41 See Ewald in the Nothnagel System. 
"Kast, Kongr., f. in. Med., 1896, p. 161. 
43 Osier, Am. Jour. Med. Sci., vol. cxiv. p. 377. 



NUTRITION AND METABOLISM 335 

or cured many patients with this disease, and that the adminis- 
tration of large quantities of thyroid substance to a normal 
individual will produce symptoms somewhat resembling those 
of exophthalmic goitre. 

THE QUALITATIVE CHANGES IN METABOLISM. 

Unfortunately, we know but little concerning the inter- 
mediary stages through which the various constituents of the 
body pass before they are finally eliminated through the ex- 
cretory organs as highly oxidized products. Though it would 
be logical to discuss the catabolism of each substance sepa- 
rately, and to follow each to its excretion, this is not possible 
with our present limited knowledge. We shall therefore 
merely consider, first, certain facts concerning the proteids, 
and, later, certain abnormal excretory products. 

The proteids taken in the food are split up in the body 
into nitrogenous and non-nitrogenous constituents. The for- 
mer probably consist of ammonium compounds, and the greater 
part of these are synthesized into urea, probably in the liver, 
and are then eliminated through the kidneys. Nitrogen is 
present in the urine in various forms; about eighty-five per 
cent, being urea, from two to five per cent, being ammonia, 
and the remaining ten per cent, being made up of a variety 
of compounds of which uric acid and the purin bases form a 
large part. 

Whether or not the proteid catabolism in the body follows 
the same course as it does in the digestive tract — viz., albu- 
moses, peptones, and amido-acids — has not yet been deter- 
mined. Pathologically, at least, albumoses may be formed, 
for they are demonstrable in the urine, as will be shown in 
discussing the subject of fever (p. 388). 

Autolysis. — If the organs of the body are kept aseptically 
at 37 C. for some time, their proteids undergo hydrolytic 
cleavage, owing to the action of enzymes that are present in 



336 CLINICAL PATHOLOGY 

the cells. 44 Albumoses have not been demonstrated as 
products of this " autolysis," presumably because they are so 
rapidly split up into amido-acids, basic substances, fatty acids, 
hydrogen sulphide, carbohydrates, etc. The nucleo-proteids 
are decomposed into proteids and the nucleinic acids, and the 
latter decompose again into phosphoric acid and the purin 
bases. It is an interesting fact that the enzymes in any par- 
ticular class of cells will split up the proteids of those cells 
more readily than they will split proteids from other sources. 
To what extent the cleavage of proteids within the normal 
body resembles autolysis is not known, for normally the inter- 
mediary products of proteid catabolism, such as the amido- 
acids, do not appear in the urine. 

The products of a hydrolytic cleavage of proteids are, how- 
ever, excreted under pathological conditions, especially when 
dead cells or fibrin are left to themselves ; as occurs in 
abscesses, in the resolving stage of pneumonia, 45 in acute 
yellow atrophy of the liver, and in phosphorus poisoning. In 
all of these, albumoses and even peptones may appear in the 
urine. 46 

Since the above conditions are caused by toxic or infec- 
tious processes, the question naturally arises as to whether the 
hydrolytic cleavage of the proteids is due directly to the 
toxins or bacteria that cause the disease, or whether it is due 
to the action of the intracellular enzymes and is of the nature 
of an autolysis. The former view seems rather improbable, 
for Miiller has shown that the pneumonic exudate exhibits no 
tendency to undergo hydrolytic cleavage so long as but few 
leucocytes are present, even though the bacteria have been 

44 Salkowski, Deut. Klinik., vol. xi. p. 147. 

46 F. Miiller, Kongr. f. in. Med., 1902, p. 192 ; Simon, Arch. f. klin. 
Med., vol. lxx. p. 604. 

40 For pneumonia, see Ito, Arch. f. klin. Med., vol. lxxi. p. 29; for 
albumosuria in general, see Stadelmann, Untersuchungen iiber Peptonuria, 
Wiesbaden, 1894. 



NUTRITION AND METABOLISM 337 

there all the time. As has been already mentioned, the tissues, 
free of all bacteria, contain proteolytic enzymes, and it seems 
probable that these are responsible for the abnormal decom- 
positions in the above-mentioned conditions. 

During the involution of the puerperal uterus the muscle- 
fibres also undergo autolysis, 47 and the resulting products may 
appear in the urine. 48 

In many diseases of the liver no abnormal end-products 
of proteid decomposition are excreted. In other more serious 
hepatic conditions, various pathological substances appear, 
and in acute yellow atrophy and phosphorus poisoning, espe- 
cially, the urine may contain albumoses, 49 or even peptones, 50 
as well as leucin, tyrosin, para-oxyphenylacetic acid, and 
lysin. 51 These substances appear to arise mainly from an 
autolysis of the liver cells, but in some cases the quantity in 
the blood is so great that they could not possibly have all 
originated in this manner, and some must have come from 
other tissues. 52 

The Formation and Excretion of Ammonia. — Normally, 
from two to five per cent, of the total nitrogen excreted appears 
in the urine in the form of ammonium salts. Under patho- 
logical conditions, however, the proportion may be greatly in- 
creased, and in acute yellow atrophy, for example, it may 
even reach thirty-seven per cent. 

An increased excretion of ammonia is not the result of 
an increased production of this compound within the body ; 
for large quantities of the ammonium salts of organic acids 

47 Langstein and Neubauer, Miinch. med. Wochens., 1902, p. 1249. 

"Ehrstrom, Arch. f. Gyn., vol. Ixiii. p. 695. 

"v. Jaksch, Ztft. f. klin. Med., vol. vi. p. 413; Robitschek, Deut. med. 
Wochens., 1893, No. 24. 

°°Miura, Virch. Arch., vol. ci. p. 317. 

" Neubcrg and Richter, Deut. med. Wochens., 1904, No. 14. 

" A. E. Taylor, Jour, of Med. Research, vol. viii. p. 424 ; Neuberg and 
Richter, Deut. med. Wochens., 1904, p. 499. 

22 



338 CLINICAL PATHOLOGY 

may be taken by the mouth with only an insignificant increase 
in their elimination in the urine. 53 The quantity of ammonium 
salts in the urine is to be regarded rather as an indication of 
an excessive quantity of acid in the body. The ammonia 
normally formed in metabolism, instead of being transformed 
into urea, combines with the excessive acids, and is excreted 
by the kidneys as the ammonium salts of these acids. For 
example, Walter 54 found that, after administering hydro- 
chloric acid to dogs, about three-fourths of it was neutralized 
by ammonia in the body, while most of the remainder went 
to raise the acidity of the urine, and a small part apparently 
combined with the fixed alkalies of the blood. This last effect 
is serious, for the ability of the blood to carry carbon dioxide 
is thereby diminished (see p. 228). 

An excessive excretion of ammonia is indicative, therefore, 
of an excessive amount of acid in the body. The amount of 
ammonia in the urine is increased whenever the proteids of 
the diet are increased at the expense of the carbohydrates, 
for the reason that proteids furnish an acid ash. The amount 
is increased, furthermore, whenever there is a pathological 
breaking down of the tissues, for this is equivalent to an 
increased proteid catabolism. In diabetes, an excessive amount 
of organic acids may be formed, thus increasing the elimina- 
tion of ammoniun^ salts. 55 Finally, an abnormal excretion of 
ammonia may accompany various chronic diseases, especially 
of the liver. 

That the increased elimination of ammonia is purely 
secondary has been proved by the fact that, if alkalies be 
administered to patients who excrete excessive quantities of 
ammonia in the urine, the abnormal acid in the body will be 

53 Rumpf, Kongr. f. in. Med., 1896, p. 509 ; also Virch. Arch., vol. 
cxliii. p. 1. 

M Arch. f. exp. Path., vol. vii. p. 148. 
05 Rumpf, Virch. Arch., vol. cxliii. p. 1. 



NUTRITION AND METABOLISM 339 

neutralized, the excessive excretion of ammonium compounds 
diminished, and the excretion of urea correspondingly in- 
creased. 

In some instances the origin of the abnormal acidity is 
readily determined. Mineral acids may have been taken by 
mouth, either accidentally or with suicidal intent. In phos- 
phorus poisoning, the rapid destruction of cell protoplasm 
liberates the sulphur and phosphorus contained in the proteid 
molecules, and these give rise to sulphuric and phosphoric acids 
in considerable quantities. In addition to these, various 
organic acids, such as lactic and aromatic acids, are formed 
in phosphorus poisoning, and this excessive acid production is 
sufficient to account for the increased excretion of ammonia 
which takes place in this condition. In many diseases, how- 
ever, we can only surmise the cause of the excessive production 
of acids in the body. 

The Production of Organic Acids. — Organic acids, espe- 
cially carbonic and carbamic acids, are being constantly 
formed in normal metabolism. These particular acids, how- 
ever, are not eliminated in ammonia combinations, for the 
carbonic acid leaves the body, for the most part, through the 
lungs, and the ammonium salt of carbamic acid can be trans- 
formed into urea in the liver. The organic acids that are 
most frequently eliminated as ammonium compounds are 
/5-oxybutyric and diacetic acids. 

It is remarkable that sarcolactic acid is not more frequently 
found in the urine, for we know that it is normally formed 
in considerable quantity during muscular activity. Under 
such circumstances, however, it is apparently rapidly oxidized. 
It probably arises from the non-nitrogenous products of pro- 
teid cleavage, although it is possible that it may also arise in 
part from the carbohydrates. Pathologically, lactic acid has 
been found in the urine in cases of phosphorus poisoning, 50 
" v. Noordcn, Stoffwcchsclpathologie, p. 294. 



340 CLINICAL PATHOLOGY 

in trichinosis, 57 in pernicious anaemia, in severe heart disease, 
acute yellow atrophy, and typhoid fever, 58 and in animals 
during arsenical poisoning. 59 Yet in none of these conditions, 
with the possible exceptions of phosphorus poisoning and 
acute yellow atrophy, does lactic acid regularly appear in the 
urine. In some, its appearance is possibly due to a diminution 
in the oxidative processes within the body; in others, to dis- 
ease of the liver; and, in still others, to unknown causes. 
yEthyliden-lactic acid has been found in the urine in severe 
cases of diabetes, and at times proprionic and acetic acids have 
also been found. 

Of all the organic acids, /?-oxybutyric is the most im- 
portant in this respect, for it appears in the urine not so very 
infrequently, and sometimes it is excreted in enormous quan- 
tities. If this acid be oxidized, it is transformed into diacetic 
acid, and later into aceton, so that these three substances are 
very closely related, and they have been collectively termed 
the aceton bodies. 60 All three are excreted by the kidneys, 
and, in addition, aceton may leave the body with the expired 
air, giving a characteristic " fruity" odor to the breath. Nor- 
mally, these aceton bodies are oxidized to carbon dioxide and 
water in the body, and only traces, at most, of aceton are 
normally excreted in the urine. Under various abnormal con- 
ditions, however, they may leave the body unoxidized. This 
may occur during hunger, 61 during a salt-free diet, 62 in many 
cases of diabetes, 63 and in some cases of fever 64 and of car- 



57 Wiebel, Ber. k. k. chem. Gesellsch., 1871, p. 139. 
68 v. Noorden, loc. cit. 

58 H. Meyer, Arch. f. exp. Path., vol. xvii. p. 304. 
80 Waldvogel, Die Acetonkorper, Stuttgart, 1903. 
01 Lehmann, Miiller, et al., Virch. Arch., vol. cxxxi. Suppl. 
62 A. H. Taylor, Univ. of Cal. Publications, Pathology. 

03 Stadelmann, Arch. f. exp. Path., vol. xvii. p. 419 ; Minkowski, ibid., 
vol. xviii. p. 35. 

64 Kulz, Ztft. f. Biol., vol. xxiii. p. 165. 



NUTRITION AND METABOLISM 341 

cinoma. 65 Experimentally, /5-oxybutyric acid may appear in 
the urine of dogs after phloridzin poisoning and after extir- 
pation of the pancreas, 66 though the latter is rare. At times 
some one or several of these compounds, but especially aceton, 
will appear in the urine without any cause. 67 It is possible, 
in these obscure cases, that it arises from the absorption of 
toxic substances from the intestines. It was formerly held 
that the aceton bodies might be formed within the intestinal 
canal, but at present there is but little inclination to refer their 
origin to this source. In the majority of cases, at least, they 
are produced during the intermediary metabolism within the 
body. 

No strict parallelism seems to exist between the amount 
of aceton bodies and the rapidity of proteid decomposition, 
and it is possible, for example, to find /?-oxybutyric acid in 
the urine at a time when the body is in nitrogenous equili- 
brium. 68 

One important cause that leads to the formation of the 
aceton bodies is a diminution in carbohydrate metabolism with 
an increased destruction of fats. For this reason, they are very 
apt to appear in the urine during fasting; and it has been 
shown that the administration of fats and especially of fatty 
acids by the mouth increases their elimination. 69 Many favor 
the view that aceton, diacetic acid, and /?-oxybutyric acid are 
all derived from the breaking down of fat in the body; but, 
owing to our ignorance as to the relation that exists between 
the carbohydrates, the fats, and the non-nitrogenous cleavage 
products of the proteids, it is impossible at present to reach a 
final verdict on this question. 

" Klemperer, Berl. klin. Wochens., 1889, No. 40. 

M v. Mering, Ztft. f. klin. Med., vol. xvi. p. 431; Minkowski, Arch. f. 
exp. Path., vol. xxxi. p. 85. 

" Lorenz, Ztft. f. klin. Med., vol. xix. p. 18. 

M Weintraud, Arch. f. exp. Path., vol. xxxiv. p. 169. 

"Joslin, Jour, of Med. Research, vol. xii. p. 433. 



342 CLINICAL PATHOLOGY 

In no disease do the aceton bodies appear in the urine in 
such large quantities as they do in some cases of diabetes 
mellitus. Their formation in this condition is undoubtedly in 
part dependent upon an inability to consume carbohydrates 
normally and upon the resulting excessive consumption of 
fats ; yet these factors are certainly not the only ones present, 
for in many severe cases of diabetes the aceton bodies are 
absent from the urine. This appears to be especially true of 
pancreatic diabetes. 70 

The Effects of an Excessive Formation of Organic Acids. 
Diabetic and Other Toxic Comas. — The specific action of the 
aceton bodies is a comparatively slight one. Aceton, in large 
doses, will produce a sort of drunkenness, similar to that 
caused by alcohol, and it is possible that in certain intestinal 
diseases of children it may cause a feeling of fatigue. The 
effect produced by ,3-oxybutyric and diacetic acids is, for the 
most part, not a specific toxic effect of these compounds, but 
is due to their acid properties. (That this is not altogether 
true is proved by the fact that neutral salts of /3-oxybutyric 
acid are somewhat toxic to rabbits. 71 — Ed.) In virtue of their 
acid properties, these organic acids will combine with basic 
substances in the body, and they tend to carry them away in 
the urine. In this manner they produce the symptoms of an 
acid intoxication (see p. 228). 

In the comas that accompany diabetes, carcinoma, and 
some intestinal diseases, large quantities of /?-oxybutyric acid 
are usually eliminated in the urine. The patient becomes stupid 
and sleepy or, at times, irritable. The temperature falls, the 
respirations become deep and often more frequent, and the 
heart's action becomes rapid. 

The immediate cause of diabetic coma is unknown, but it 
seems to be precipitated in some instances by a too rigorous 

"Liithje, Personal communication. 

71 R. Wilbur, Jour, of the Am. Med. Assoc, 1904, p. 1228. 



NUTRITION AND METABOLISM 343 

meat diet, or, again, by digestive disturbances. The symp- 
toms are certainly very similar to those that result from acid 
intoxications experimentally produced, and in no other condi- 
tion are such enormous quantities of ,5-oxybutyric acid found 
in the urine as at the onset of diabetic coma. The ability of 
the blood to carry carbon dioxide is usually found to be con- 
siderably diminished 72 during diabetic coma, just as it is in 
experimental acid intoxications (see p. 228). These facts 
indicate the acid character of the intoxication. 

On the other hand, in some comas, complicating diabetes, 
no increased elimination of acids has been found. 73 Yet 
such cases are quite rare ; and, as a rule, the symptoms of 
diabetic coma are accompanied by an acid intoxication. 74 The 
coma is preceded by an increased formation of ,3-oxybutyric 
acid in the body, and large quantities of this acid may appear 
in the urine as the ammonium salt. During the coma, how- 
ever, the elimination frequently does not keep pace with the 
acid formation, and consequently considerable amounts are re- 
tained in the body. Careful estimations of the amounts thus 
retained demonstrate that they are sufficient to give rise to 
coma. In some cases, it is possible to abort the coma, partly or 
completely, by the use of large quantities of soda, which serves 
to neutralize the acid in the body. 75 

Those rare cases of diabetic coma without increased acid 
formation are, according to Naunyn, produced by other toxic 
substances, which directly act upon the cerebral cells, and espe- 
cially upon the cells of the respiratory centre. The exact 
nature of these toxic substances is unknown, but from the 
diversity of symptoms seen in diabetic coma it is readily con- 
ceivable that more than one cause is operative. 

" Kratfs, Ztft. f. Heilkundc, vol. x. p. 106. 

7 ' Kraus, loc. cit. ; Rumpf, Bcrl. klin. Wochens., 1895, Nos. 31 and 32. 
7< Magnus-Levy, Arch. f. exp. Path., vol. xlii. p. 149 ; vol. xlv. p. 389. 
"Liithje, Ztft. f. klin. Med., vol. xliii. p. 225. 



344 CLINICAL PATHOLOGY 

The Relation between Hepatic Disease and the Excretion 
of Ammonia. — The greater portion of the nitrogenous waste, 
which does not serve to neutralize acids, leaves the body in 
the form of urea. We know that the liver can convert many 
ammonium salts, such as the carbamates, into urea, and Min- 
kowski's experiments on birds would seem to indicate that 
this is a portion of the normal hepatic function. 76 On the 
other hand, we are not certain that all the eliminated urea is 
thus formed in the liver, nor, indeed, that it is all derived from 
ammonium salts. 

These questions are of the greatest importance, for it is 
possible that some relation may exist between hepatic diseases, 
on the one hand, and the amount of urea formed out of am- 
monium salts, on the other. Not infrequently it happens that 
the liver is found to be diseased when large quantities of 
ammonia have appeared in the urine. We have seen that one 
cause of an increased excretion of ammonia is an acid intoxi- 
cation, in which case the ammonia serves merely to neutralize 
the excess of acid. Is it not possible, however, that large 
amounts of ammonia may be excreted for the reason that the 
liver is so diseased that it cannot form urea out of ammonium 
salts? Such a serious loss of function could only result from 
a most extensive destruction of liver cells, if we may draw any 
analogy from the corresponding effects produced by diseases 
of the pancreas and of the thyroid gland. 

An increased excretion of ammonium compounds at the 
expense of urea has been observed in different forms of hepatic 
disease, such as cirrhosis, tumors, and extensive degenerations, 
though these urinary changes do not accompany all serious 
diseases of the liver. 77 Weintraud discovered that if ammo- 
nium salts were administered to patients, even in the advanced 
stages of hepatic disease, these salts were converted into urea 

76 Minkowski, Arch. f. exp. Path., vol. xxxi. p. 214. 

77 Weintraud, ibid., p. 30 ; Munzer, ibid., vol. xxxiii. p. 180. 



NUTRITION AND METABOLISM 345 

just as they are in healthy individuals; thus demonstrating 
that these patients are still able to transform large quantities 
of ammonium salts. It therefore seems very probable that 
the excessive ammonia in their urine is due to an abnormal 
production of acids in their bodies. As yet, however, their 
elimination of acid substances has not been sufficiently investi- 
gated. If the excretion of ammonium salts could be decreased 
by the administration of fixed alkalies, then we could feel 
fairly certain that in all these hepatic diseases we were again 
dealing with a primary acid intoxication, similar to that 
present in diabetic coma. 

Alkaptonuria. — The tyrosin and phenylalanin groups of 
the proteid molecules at times give rise to the formation of 
dioxyphenylacetic acid (homogentisic acid), and to dioxy- 
phenyl-lactic acid (hydrochinonlactic acid). When these acids 
are excreted by the kidneys, the urine turns dark on standing 
or on the addition of alkalies, and the condition is termed 
alkaptonuria. 78 These urines will reduce Fehling's solution, 
and the condition may be mistaken for a glycosuria. Patients 
with alkaptonuria show no other clinical peculiarities, save 
occasionally a pigmentation of the cartilages in various parts 
of the body. Although the belief was held at one time 
that the substances giving rise to the reaction for alkapton 
were produced in the intestines, it now seems certain that these 
oxyacids arise within the body during intermediary meta- 
bolism, and that they appear in the urine because the organism 
is unable to break down the tyrosin and alanin groups of the 
proteid molecule in a normal manner. If tyrosin be admin- 
istered to these patients, it appears in the urine as alkapton, 
and, since tyrosin is believed to be one of the products of 

"Baumann and Wolkow, Ztft. f. physiol. Chcm., vol. xv. p. 228; E. 
Meyer, Arch. f. klin. Med., vol. lxx. p. 443; Langstein and Meyer, ibid., 
vol. lxxviii. p. 161; Mittclbach, ibid., vol. lxxi. p. 50; Abderhalden and 
Falta, Ztft. f. physiol. Chem., vol. xxxix. p. 143. 



346 CLINICAL PATHOLOGY 

normal proteid catabolism, the amount of alkapton which ap- 
pears in the urine in these patients is an indication of the 
amount of proteid metabolism. The real reason why the body- 
is unable to break down the tyrosin group is unknown to us, 
as is the organ in which this group is transformed into the 
alkapton acids. 



CHAPTER VIII. 

DISTURBANCES IN CARBOHYDRATE METABOLISM. DIABETES. 

In this chapter we shall limit our discussion to dextrose 
or grape-sugar ; for, although other sugars, such as levulose 1 
and pentose 2 may appear in the urine, nevertheless the mean- 
ing of these findings is not yet sufficiently clear to be discussed 
in connection with dextrose. 

The cells of the body that use dextrose, especially the 
muscle-cells, take it out of the blood; yet the amount in the 
plasma remains nearly constant, for whenever the percentage 
falls below the normal, new sugar is supplied to the blood, 
mainly from the glycogen storage in the liver. The liver gly- 
cogen is derived, for the most part, from the carbohydrates, 
and, to a lesser extent, from the proteids taken in the food. 
The sugar that is absorbed from the intestines goes to the 
liver by way of the portal vein, and is there converted into 
glycogen by a process of dehydration and polymerization. 
The non-nitrogenous products of proteid cleavage may also 
apparently be converted into glycogen by a synthetic process, 
though this is denied by some. 3 The liver acts, therefore, as 
a store-house for carbohydrate material, holding it back when 
it is present in the blood in excess, and giving it out when the 
percentage falls. 

In a healthy man the sugar in the blood varies but little, 
the quantity remaining constantly in the neighborhood of o.i 
to 0.2 per cent. If, for any reason, more than this is present 
in the general circulation without 1 icing immediately consumed, 

1 Miiller, Path, der Ernahrung, p. 232. 

2 Kulz & Vogel, Ztft. f. Biol., vol. xxxii. p. 185; Salkowski, Berl. klin. 
Wochens., 1895, No. 17; Blumcnthal, ibid., No. 26. 
a Pfliiger, Pfliigcr's Arch., vol. xcvi. 

347 



348 CLINICAL PATHOLOGY 

it is eliminated by the kidneys, and the urine then contains 
more than the trace of dextrose normally present. 

Alimentary Glycosuria. — As we have said, the liver pos- 
sesses the property of removing from the portal blood any 
excessive quantity of sugar that may be present there. If, 
for example, a limited quantity of dextrose be injected into 
the portal vein, the excess disappears from the blood ; whereas, 
if the same quantity be injected into a systemic vein, the per- 
centage in the general circulation is increased and sugar is 
excreted by the kidneys. 4 

Yet, when very large amounts of dextrose are taken by 
mouth and are absorbed from the intestinal canal within a 
short space of time, the percentage in the blood may rise above 
the normal, either because the liver cannot stop all the sugar 
coming to it through the portal vein or because some sugar 
reaches the general circulation through the lymphatics with- 
out traversing the liver. 5 Under such circumstances dextrose 
may be excreted by the kidneys, and we speak of this condition 
as an alimentary glycosuria. The quantity of sugar that must 
be taken by mouth in order to produce an alimentary glyco- 
suria varies in different individuals. 6 It does not necessarily 
follow, however, that a certain person is in an early stage of 
diabetes merely because he passes dextrose in the urine after 
taking a relatively small quantity by mouth. 7 Yet such may 
be the case. Minkowski has shown, for example, that whereas 
the removal of the whole of the pancreas is followed by a 
diabetes, the removal of a part may cause merely an inability 
to take much sugar in the food without having it appear in 
the urine. Furthermore, clinical experience has demonstrated 

* Schopffer, Arch. f. exp. Path., vol. i. p. 72>- 
5 Ginsberg, Pfliiger's Arch., vol. xliv. p. 306. 

6 Hofmeister, Arch. f. exp. Path., vol. xxv. p. 240; see v. Noorden, 
Pathologie der Soffwechsels, p. 391. 

7 Strauss, Deut. med. Wochens., 1897, Nos. 18 and 20. 



DIABETES 349 

that, in some cases, a marked alimentary glycosuria gradually 
passes on into a true diabetes mellitus. 

The occurrence of an alimentary glycosuria in a healthy 
man is greatly favored by alcoholic drinks, and especially by 
the ingestion of large quantities of beer. s It is impossible to 
say why this should be so, and whether the effect, in the case 
of beer, is to be attributed more to its alcohol or to its maltose. 

Lactose may also appear in the urine after excessive quan- 
tities have been taken in the food, but it appears there more 
frequently because it has been resorbed from the mammary 
glands of nursing women, owing to a stasis of milk. Some 
special factor seems to favor its excretion in these cases, for 
the amount absorbed would appear to be too small to give 
rise to an ordinary alimentary glycosuria. 

Many studies have been made upon the ease with which 
an alimentary glycosuria may be produced in different diseases. 
Apparently, it is most apt to follow the ingestion of a small 
quantity of sugar when the patient is suffering from phos- 
phorus poisoning or from some infectious disease, and an 
alimentary glycosuria is easily produced in certain patients 
with exophthalmic goitre and with various neuroses. Hepatic 
diseases apparently do not especially favor the development of 
a glycosuria after the administration of ordinary dextrose, 
but they frequently diminish the patient's ability to eat levu- 
lose without having it appear in the urine (alimentary levulo- 
suria). 9 

Phloridzin Glycosuria. 10 — The glycosuria that follows the 
administration of phloridzin is peculiar, in that, according to 





Striimpell 


Berl 


klin. 


Wochens., 1896, No. 47 


; Krehl, Ztrbl. f 


in Med., 


1897, 


p. 103. 












t 


Strauss, Deut. 


med. 


Wochcns., 1901, Nos. 


44 and 45 ; Cha 


es, ibid., 


1904 


No. 19. 














See v. Mcring, 


Kongr. f. in Med., 1886, p. 


1X5; Minkowski, 


Arch. f. 


exp. 


Path., vol. 


xxxi 


P-85 


; papers by Lusk et al. 


in Am. Jour, of 


Physiol., 


vols. 


i., Hi., be., 


and 


X. 









350 CLINICAL PATHOLOGY 

most observers, it is accompanied by a normal or reduced per- 
centage of dextrose in the blood. 11 Chemically, phloridzin is 
a glucoside, — i.e., it is capable of being split up into dextrose 
and a proteid radicle. The amount of dextrose that appears 
in the urine after the administration of phloridzin, however, 
is so great that it cannot be accounted for by a mere splitting 
of the glucoside, and it is certain that the administration of 
this substance will result in an actual removal of dextrose from 
the body. In what manner is this accomplished? According 
to one view, the resulting glycosuria is caused by some altera- 
tion in the cells of the kidneys, whereby they become perme- 
able for the sugar normally present in the blood. According 
to another view, however, the glucoside decomposes in the 
kidneys and the glucose derived from it is eliminated. The 
other product of the decomposition, phloretin, then combines 
with the glucose of the blood and is again decomposed in the 
kidneys, and thus, by acting as a carrier of glucose, phloridzin 
may cause the excretion of large quantities of sugar. 

In phloridzin poisoning the sugar excreted is derived, first 
of all, from the glycogen of the liver, which early disappears. 
It seems probable that it may also be derived from the proteids 
of the body, for it is known that glucose continues to be ex- 
creted in phloridzin poisoning, even though the animal be 
fasting and its liver presumably free of glycogen. At any rate, 
the proteid decomposition is accelerated under these circum- 
stances, and even ,5-oxybutyric acid may be excreted. 12 If 
phloridzin be given to fasting animals, a fatty degeneration 
of the liver is produced, which can be prevented if the animal 
be fed on proteids or carbohydrates. 13 At times the amount 
of sugar excreted after taking phloridzin is so great that it 

11 In opposition, see Pavy, Jour, of Physiol., vol. xx,, and Pfiuger, 
Pfliiger's Arch., vol. xcvi. p. 383. 

12 Praussnitz, Ztft. f. Biol., vol. xxix. p. 168. 
u Rosenfeld, Ztft. f. klin. Med., xxviii. p. 256. 



DIABETES 351 

seems as if it must be formed in part from the fats of the 
body, 14 a possibility that will be considered in another place 

(P. 356). 

Renal Diabetes. — The glycosuria of phloridzin poisoning- 
is therefore characterized by the fact that the amount of sugar 
in the blood is not increased; and it seems probable that in 
this condition, as well as in certain cases of marked diuresis, 15 
the resulting glycosuria is due to an inability on the part of 
the renal cells to hold back the sugar normally present in the 
blood. Little is known about such conditions in man, but 
recent observations have tended to show that glycosuria may 
result from just such a renal insufficiency. To these cases 
has been given the name of renal diabetes. 16 Luthje has 
shown that the sugar was present in the blood of his patient 
in less than the normal quantity, thus demonstrating that the 
glycosuria was due to some abnormal permeability on the 
part of the kidneys toward dextrose. The amount of sugar 
excreted by such patients is independent, to a great extent, 
of the amount taken in the food; yet this is not especially 
characteristic of renal diabetes, for the same is true of certain 
forms of diabetes mellitus. 

Transient Glycosurias. — Glycosurias, lasting only a few 
hours or days, 17 have been observed after various intoxications, 
infections, injuries, and diseases of the central nervous system. 

Of these transient glycosurias, the best studied is that 
which results from a puncture of a certain limited area in the 
floor of the fourth ventricle of animals. 18 In these cases the 
appearance of sugar in the urine is always preceded by an 

u Rumpf, Hartogh, and Schumn, Arch. f. exp. Path., vol. xlv. p. II. 

"Jacobi, Arch. f. exp. Path., vol. xxxv. p. 213; O. II. Brown, Am. 
Jour, of Physiol., vol. x. p. 378. 

10 G. Klemperer, Bcrl. klin. Wochens., 1892, No. 49; Naunyn, Diabetes, 
p. 106; Liithjc, Munch, med. Wochens., 1901, No. 38. 

" Bohm and Hoffman, Arch. f. exp. Path., vol. viii. p. 297. 

ls Claude Bernard, Pfluger, Pfliiger's Arch., vol. lxxxvi. pp. 303, 360. 



352 CLINICAL PATHOLOGY 

increase in the amount present in the blood, and it is favored 
by a large store of glycogen in the liver. If glucose be injected 
into a mesenteric vein in these animals, it is not taken up by 
the liver as it normally should be, but it passes into the general 
circulation and is then excreted by the kidneys. If the splanch- 
nic nerves be cut, or if the liver be removed, a puncture of the 
fourth ventricle has no effect upon the urine. All these facts 
seem to indicate that the glycogen of the liver is the source 
of the excessive amount of sugar in the blood and that the 
nervous lesion causes the glycosuria by influencing, in some 
manner, the glycogenic function of the liver. 

The glycosurias that may accompany morphine and curare 
poisoning are apparently of a similar nature. 

DIABETES MELLITUS. 

Diabetes mellitus is characterized by a glycosuria that is 
not due to any of the above-mentioned causes, and especially 
not to the ingestion of large amounts of grape-sugar. Usually 
the dextrose is constantly present in the urine, but it may only 
be found there periodically. In some cases of diabetes, levu- 
lose also appears in the urine. 19 The glycosuria of diabetes 
mellitus always results from an excessive amount of sugar in 
the blood, a hyperglycemia. Instead of the normal percentage 
of o.i to 0.2, it may rise even to 0.7 per cent. 

Mild and Severe Diabetes. — In the milder forms of dia- 
betes, sugar does not appear in the urine if no carbohydrates — 
i.e., sugars, starches, etc. — are taken in the food. Great indi- 
vidual variations exist as to the quantity of carbohydrate 
material that must be taken in order to produce glycosuria. 
On the one hand, a patient may be able to take one hundred 
and fifty grams or more of starch in twenty-four hours without 
suffering from glycosuria; while, on the other, a glycosuria 

19 May, Arch. f. klin. Med., vol. lvii. p. 279 ; Rosin and Laband, Ztft. 
f. klin. Med., vol. xlvii. p. 182; Naunyn, Diabetes. 



DIABETES 353 

may result when only twenty-five to thirty grams are taken. 
Not all carbohydrates show the same tendency to cause glyco- 
suria in these patients, and many, for example, will tolerate 
lactose in the food even better than starch. 

This mild form of diabetes is distinguishable from alimen- 
tary glycosuria by the fact that starch is not tolerated; for, 
so far as we know, a mere excess of starch in the diet of a 
normal individual never leads to the excretion of an abnormal 
quantity of sugar in the urine. Possibly, however, exceptions 
do occur to this rule, notably in the case of infectious diseases. 

In the more severe forms of diabetes, sugar is excreted in 
the urine even when no carbohydrates are taken by mouth, 
and in some, the most severe cases, the glycosuria even con- 
tinues when the patient is fasting. 

It was formerly believed that this distinction between mild 
and severe cases of diabetes was a sharp one, and that it rested 
upon fundamental differences in the tissues. In the mild cases 
the body was unable to assimilate carbohydrate material intro- 
duced as such, but was able to consume the carbohydrate mole- 
cules split off from the proteids, whereas, in the severe cases 
neither could be utilized. Yet we now know that no such sharp 
distinction can be drawn, that the one condition shades into 
the other, and that, finally, the body may be able to consume 
a considerable proportion of the carbohydrates taken in the 
food, even though the diabetes is so severe that glycosuria per- 
sists during fasting. Notwithstanding these facts, the above 
distinction has a certain clinical value, and a case of diabetes 
can hardly be considered a mild one if the body is unable to 
assimilate a certain amount of carbohydrate material in the 
food without the excretion of sugar in the urine. 

Derivation of Sugar from Proteids and Fats. — The sugar 
that appears in the urine in these severe cases of diabetes, when 
the patient is on a diet free of ordinary carbohydrates, is 
derived either from the glycogen or substances resembling 

23 



354 CLINICAL PATHOLOGY 

glucosicles within his own body, 20 or from the proteids or fats 
of the food or of the body. That sugar may be derived from 
proteids is a view widely accepted by both pathologists and 
physiologists. The amount excreted in severe cases of dia- 
betes may be so great as to render it improbable that it could 
all have come from preformed carbohydrate groups of atoms 
within the proteid molecule. It is necessary to assume in 
these cases that the sugar has been synthesized in the body 
from other groups of atoms contained within the proteid mole- 
cules. Casein, for example, does not contain such preformed 
carbohydrate groups, yet its administration to certain diabetics 
increases the elimination of sugar as much or even more than 
does the administration of an equal quantity of proteids known 
to contain preformed carbohydrate groups. 21 

This view that sugar may arise from proteids containing 
no preformed carbohydrate groups has been strenuously op- 
posed by Pfliiger. 22 He considers that all the sugar excreted 
in the urine is derived from carbohydrates or from carbo- 
hydrate groups in the proteid molecules. It does not lie within 
our province to discuss the purely physiological side of this 
question; yet it seems proper for us to review some of the 
evidence bearing upon the question as to the ability of the 
pathological diabetic organism to form sugar out of proteids. 

We possess no accurate data as to the quantity of glycogen 
stored up within the bodies of diabetic patients, and Pfliiger 
has shown that the quantity is often underestimated. Never- 
theless, a great number of observations would seem to indi- 
cate that the quantity of glycogen in the liver is diminished 
in diabetes. 23 If this were so, then the amount of sugar that 

20 Pfliiger, Pfliiger's Arch., vol. xcvi. 

21 Liithje, Ztft. f. klin. Med., vol. xxxix. p. 397; vol. xliii. p. 225. 

22 Pfliiger's Arch., vol. xlvi. p. 1. 

23 See Kiilz, Pfliiger's Arch., vol. xiii. p. 267 ; v. Mering, ibid., vol. 
xiv. p. 274; Abeles, Zentralbl. f. die med. Wissen., 1885, No. 26; Naunyn, 
Diabetes. 



DIABETES 355 

patients with severe diabetes may excrete after the adminis- 
tration of casein admits of hardly any other interpretation 
that that it is derived from proteids. 24 In dogs from which 
the pancreases have been removed this is even more clear, for 
the glycogen in their livers and muscles is always small, and 
during fasting it practically disappears. 25 Yet if casein be 
given to these fasting dogs, sugar is immediately excreted in 
the urine in quantities corresponding to the quantities of 
casein that they have taken. 26 Pfliiger would explain many 
such observations by assuming that the subject of the experi- 
ment secretly took carbohydrates; yet, although this may 
have occurred in a limited number of instances, it is highly 
improbable that it could have occurred in all; and, to us, at 
least, it seems practically certain that diabetics may form sugar 
out of proteids that contain no preformed carbohydrate atomic 
groups. 27 

It is not fully known in what parts of the body the sugar 
is formed from proteids. The liver is certainly one site of 
such transformation, and possibly the muscles may exercise a 
similar function. 

Even though we thus assume that sugar may arise from 
proteids, obscure cases still remain. One hundred grams of 
proteid material could, at most, give rise to about one hundred 
and thirty grams of sugar and sixteen grams of nitrogen. 
The ratio of dextrose to nitrogen (D:N) under these circum- 
stances would be about 8 to i. As a matter of fact, the ratio 
(D:N), as determined in the urine of dogs from which the 
pancreases have been removed, and which were fed on a 

M Kiilz, Arch. f. exp. Path., vol. vi. p. 140. 

15 Minkowski, Arch. f. exp. Path., vol. xxxi. p. 161. 

M Liithje, Arch. f. klin. Med., vol. lxxix. p. 488; Mering, ibid., 
vol. xiv. p. 274. 

27 A similar view is expressed by F. Mtillcr, Path, der Ernahrung; F. 
Kraus, Berl. klin. Wochens., 1904, No. 1 ; Magnus-Levy, Verh. der physiol. 
Gesell. zu Berlin, 1904, Nos. 5 and 8. 



356 CLINICAL PATHOLOGY 

proteicl diet, was found to be 2.8 to 1 ; 2S though recently, both 
in animals with phloridzin poisoning and in men with very 
severe diabetes, a somewhat higher ratio has been found, — 
about 3.7 to i. 29 It has been assumed that the dogs deprived 
of their pancreases were incapable of consuming sugar, and 
that the ratio found (2.8 to 1) represented the total amount 
of sugar derived from the cleavage of the proteid molecules 
within the body. Yet this assumption has proved to be in- 
correct; for, if the dogs fast completely after the operation, 
the excretion of sugar gradually ceases, while the percentage 
in the blood returns to about normal. The bodies of these 
animals are therefore capable of consuming a limited quantity 
of sugar. 30 

In certain cases of phloridzin diabetes and of diabetes mel- 
litus 31 the ratio (D : N) has been found to be as high as 6 to 1, 
or even higher. According to one explanation, an unusual 
amount of sugar is formed out of the proteids of the body in 
these cases; according to another explanation, the fat of the 
body is converted into sugar and is excreted as such. In this 
connection, it is proper to note that during the diabetes pro- 
duced either by phloridzin 32 or by the excision of the pan- 
creas, 33 the administration of glycerin or lecithin may increase 
the output of sugar. We have no direct evidence, however, 
that sugar may arise from fats; for the administration of 
fats does not affect the glycosuria. 



28 Minkowski, Arch. f. exp. Path., vol. iii. p. 85. 

28 Mandel and Lusk, Arch. f. klin. Med., vol. lxxxi. p. 472. 

30 Luthje, Munch, med. Wochens., 1902, No. 36. 

31 v. Mering, Ztft. f. klin. Med., vol. xvi. p. 431 ; Hartogh and Schumn, 
Arch, f . exp. Path., vol. xlv. p. 11; Rumpf, Pfliiger's Arch., vol. xcvii. 
p. 98; Rosenquist, Berl. klin. Wochens., 1899, No. 28; Mohr, ibid., 1901, 
No. 36; Luthje, Ztft. f. klin. Med., vol. xliii. p. 225; Rumpf, ibid., vol. 
xlv. p. 260. 

32 Cremer, Asher-Spiro Ergebnisse, vol. i. p. 888. 

33 Luthje, Munch, med. Wochens., 1902, No. 39. 



DIABETES 357 

The Glycogenic Function of the Liver in Diabetes. — We 
have already stated that diabetes mellitus is always -accom- 
panied by an increased percentage of sugar in the blood, a 
hyperglycemia. If the sugar appear in the urine only when 
carbohydrates are taken in the food, it is possible to explain 
the condition on the assumption that the liver does not store 
up the sugar coming to it by way of the portal vein, but allows 
it to raise the percentage in the blood. The capacity of the 
liver to form glycogen seems to be diminished in most cases 
of diabetes mellitus, and in some cases more than in others; 
which accounts, in part, for the different amounts of sugar 
that are excreted by different patients when all take equally 
large quantities of starch. On the other hand, the ability of 
the liver to pick sugar out of the portal blood and to store it 
never seems to be completely lost in diabetes. In a few mild 
cases this function does not seem to be greatly affected, for 
the amount of glucose in the urine remains fairly constant, 
even though considerable quantities of starch are taken in 
the food. 

After experimental removal of the pancreas from dogs the 
capacity of the body for storing up carbohydrates is certainly 
diminished, for Minkowski has shown that in these animals 
the glycogen in the liver and muscles is always reduced, and 
that it disappears during fasting. 34 

As we have just said, the ability to ingest carbohydrates 
without having sugar appear in the urine varies greatly in 
different diabetic patients. This "assimilative capacity" may 
be influenced by various procedures, but especially by not over- 
taxing the organism with too much sugar. If, for example, 
a diabetic patient is able to take one hundred grams of bread 
daily without having glycosuria, and if he has kept within this 
limit for several months, he may then be able to take one 
hundred and twenty or one hundred and forty grams of bread 
M Minkowski, Arch. f. exp. Path., vol. xxxi. p. 161. 



358 CLINICAL PATHOLOGY 

with impunity. In this manner diabetic patients may be greatly 
benefited by treatment. 

In severe cases of diabetes, the patient frequently excretes 
much more sugar than would correspond to the carbohydrates 
taken in the food, the extra sugar being derived, in all proba- 
bility, from proteids. If the formation of sugar from pro- 
teids is a physiological process, then we may assume that 
there is a more or less fundamental difference between the 
two forms of diabetes. In the mild form the body cannot 
assimilate fully the sugar which is derived from the carbo- 
hydrates of the food, but can assimilate that derived from the 
proteids; whereas, in the severe form the assimilation of 
sugar derived from either source is diminished. There are 
patients who appear to justify such a distinction, for they are 
able to take large quantities of proteids without the appear- 
ance of sugar in the urine, but yet they react to the smallest 
quantity of bread with a glycosuria. In such cases, at least, 
it seems as if the sugar that arises from the proteids acted 
differently from that derived from the carbohydrates. 

The Consumption of Sugar in Diabetes. — We now come 
to the question as to whether the diabetic body is able to 
burn sugar normally. Investigations on the respiratory inter- 
change of gases have furnished evidence that the oxidation 
of sugar in certain diabetic patients is diminished. 35 We know 
that when carbohydrates are completely burned, the volume 
of carbon dioxide given off is equal to the volume of oxygen 
consumed; i.e., the respiratory quotient is i.o. For the com- 
bustion of proteids and fats, however, relatively more oxygen 
is necessary; and in the case of the higher fats the ratio of 

35 Leo, Ztft. f. klin. Med., vol. xix. Supplement, p. no; ibid., Kongr. 
f. in Med., 1889, p. 354; Weintraud and Leyes, Ztft. f. phys. Chem., vol. 
xix. pp. 603, 629; F. Voit, Ztft. f. Biol., vol. xxix. p. 129; Nehring and 
Schmoll, Ztft. f. klin. Med., vol. xxxi. p. 59; Magnus-Levy, Verhand. 
d. physiol Gesell. zu. Berlin, 1904, Nos. 5 and 7. 



DIABETES 359 

carbon dioxide to oxygen is about i to 2, or 0.5. When carbo- 
hydrates are the main source of energy to the body, therefore, 
the ratio between the carbon dioxide given off and the oxygen 
absorbed approaches 1.0; whereas, when fats and proteids 
furnish most of the energy, this ratio falls. It has been found 
that diabetic patients upon an ordinary mixed diet show a 
lower respiratory quotient than do normal individuals upon 
the same diet. From this fact it may be inferred that, in 
spite of the large amount of glucose circulating in their blood, 
the utilization of carbohydrate material by diabetic patients 
is deficient, and that the most of their energy is derived from 
fats and proteids. 

It appears, also, that this change in the respiratory quo- 
tient is more marked in the severe than in the mild forms of 
diabetes ; in other words, the former burn sugar less than the 
latter. This view is also supported by the effect that muscular 
exercise has upon the excretion of sugar. In the milder forms 
of the disease, muscular exercise tends to diminish the glyco- 
suria, apparently because the body utilizes the sugar circulating 
in the blood. In the more severe cases, on the other hand, 
muscular exercise exerts but little effect upon the glycosuria, 
for the body can utilize comparatively little sugar. 

Thus we see that there is not only an insufficiency of the 
glycogen reservoirs in diabetes, which permits an excess of 
sugar to enter the circulation, but that there is, in addition, a 
lessened ability on the part of the body to burn the sugar. 

The nature of this lessened capacity for consuming sugar 
is not well understood. Unfortunately, we know little con- 
cerning the manner in which sugar is normally utilized in 
the body or concerning the intermediary stages, such as 
lactic acid or glycouronic acid, through which it may pass. 
There seems to be no general diminution in the oxidative 
ability of the body, for such substances as benzol, 30 lactic 

M Reyhcr, Diss. Dorpat., 1885. 



360 CLINICAL PATHOLOGY 

acid, 37 fat, and frequently even levulose are consumed nor- 
mally. Diabetes consists rather in a specific limitation of the 
ability to consume dextrose, and it seems as if the diabetic 
body fails especially to initiate the combustion of this sugar. 
Nor is this all. Normally, carbohydrates can be converted 
into fat in the body, but in diabetes this power is diminished 
or lost. 

We are acquainted with at least one factor that is neces- 
sary for a proper combustion of the sugar in the body. It is 
the pancreas. If this gland be extirpated from dogs, their 
ability to burn sugars is certainly diminished. 38 The same 
holds true also for carnivorous birds 39 and for reptiles and 
amphibia. 40 When a small portion of the pancreas is left at 
an operation, an alimentary glycosuria or a diabetes of the 
milder type may result, whereas, if the whole gland be excised, 
a diabetes of the severe type is the consequence. The sugar 
then accumulates in the blood, and the dextrose that is taken 
by mouth is again excreted in the urine. When an animal 
with such a pancreatic diabetes is placed on a strict meat diet, 
or when it is studied during the first few days of complete 
starvation, the ratio between the amounts of sugar and nitro- 
gen excreted in the urine (D : N) is found to be 2.8 to 1. It 
has been assumed that these animals are utterly incapable of 
burning any dextrose, and that the above ratio represents the 
total amount of sugar formed in the body from the proteid 
molecule. Yet this assumption is incorrect, for Liithje has 
shown that in the later stages of fasting the sugar will com- 
pletely disappear from the urine of these dogs and the per- 



87 Nencki and Sieber, Ztft. f. prak. Chem., vol. xxvi. 

88 v. Mering and Minkowski, Arch. f. exp. Path., vol. xxvi. p. 371 ; 
Minkowski, ibid., vol. xxxi. p. 85 ; Sandmeyer, Ztft. f. Biol., vol. xxxi. 
p. 12. 

89 Weintraud, Arch. f. exp. Path., vol. xxxiv. p. 303. 
40 Aldehoff, Ztft. f. Biol., vol. xxviii. p. 293. 



DIABETES 361 

centage of sugar in the blood will be normal. 41 From this, we 
must infer that, even without a pancreas, it is possible for an 
animal to consume a certain amount of sugar, and that the 
ratio of 2.8 to 1 does not necessarily represent the total amount 
of sugar derived from proteids. 

Pancreatic extracts do not possess any very decided action 
upon dextrose. If, however, they are mixed with extracts 
from muscular tissues, which latter alone are also inert, then 
the mixture possesses decided glycolytic properties. 42 It would 
appear from this that the pancreas produces an internal secre- 
tion which can assist the muscles in their consumption of 
sugar. 

Such, in brief, are the main facts concerning the nature 
of diabetes. Before an attempt is made to discuss them as a 
whole, however, it seems best to consider some other aspects 
of the disease. 

The Etiology of Diabetes. — The tendency to acquire dia- 
betes may be inherited, not alone from parents that have had 
the disease itself, but also from those who have had gout, 
obesity, or nervous disorders. 

Diabetes sometimes follows severe cerebral concussions 
and injuries, as well as violent fright and other psychic trau- 
mata. Arteriosclerosis and syphilis are frequently associated 
with diabetes, though we do not know whether they cause it 
by their action upon the nervous system or not. Definite 
anatomical lesions of the brain, especially when situated in 
the neighborhood of the fourth ventricle, certainly can pro- 
duce diabetes, though this is a very rare event. 

At times diabetes is accompanied by diseases of the liver 
or pancreas; yet in the great majority of cases such diseases 
are not demonstrable, either during life or at autopsy. 

The condition of the pancreas in diabetes is of especial 

41 Liitlije, Munch, incd. Wochcns., 1903, p. 1537. 
"Cohnhcim, Ztft. f. physiol. Clicm., vol. xxxi. p. 336. 



362 CLINICAL PATHOLOGY 

interest on account of the glycosuria produced by an extir- 
pation of this gland from animals. No pancreatic changes 
have been found post mortem in most diabetic patients, though, 
in some, easily recognizable changes were present. 43 If the 
pancreas is completely destroyed by disease, without leading 
to death within the first twenty-four hours, diabetes always 
develops. Primary carcinomata of the pancreas, however, 
may completely destroy the gland without producing diabetes ; 
apparently because the carcinoma itself retains some of the 
functions of the normal tissues. We have already noted 
Naunyn's analogous observation, — i.e., that a carcinoma of 
the liver may secrete bile. 

(It has been claimed recently that lesions of the islands 
of Langerhans in the pancreas cause many cases of diabetes. 
Opie, indeed, believes that more than half of all cases are of 
pancreatic origin, and that, when diabetes does result from 
pancreatic disease, an injury to the islands of Langerhans is 
responsible for the disturbance of carbohydrate metabolism. 44 
In view of these recent observations, it is necessary to regard 
the statements of the earlier writers as to the frequency of 
pancreatic changes in diabetes with a certain amount of cau- 
tion, for obviously their attention was not directed especially 
to these structures. — Ed.) 

Effects of Diabetes upon the Body. — In diabetes, a cer- 
tain proportion of the energy taken in the food is not utilized 
by the body, and it is therefore necessary to cover the loss by 
more abundant nourishment. Even in severe forms of the 
disease the loss of carbohydrates may be covered by the admin- 
istration of large amounts of fats and proteids, providing, of 
course, that the gastro-intestinal canal can absorb a necessary 

43 v. Hansemann, Ztft. f. klin. Med., vol. xxvi. p. 191 ; Hoppe-Seyler, 
Arch. f. klin. Med., vol. clii. p. 171 ; M. B. Schmdt, Munch, med. Wochens., 
1902, No. 2. 

44 Diseases of the Pancreas, 1903, p. 279. 



DIABETES 363 

amount of material. Fortunately, this is usually possible, and 
only rarely is absorption markedly reduced in diabetes. 45 The 
greater an individual's need for energy, the more difficult will 
it be to maintain his nutrition when his ability to utilize carbo- 
hydrates is lessened. Yet the combined skill of physician 
and cook will often accomplish wonders in this respect. If 
the diabetic patient absorbs sufficient nourishment, his metabo- 
lism does not, as a rule, differ from that of a healthy individual 
upon the same diet. If it is impossible to furnish sufficient 
energy to him, his fat and body proteids are consumed, just 
as those are of a healthy individual during partial starvation. 
Some diabetics consume the proteid material in their bodies 
with abnormal rapidity, being similar in this respect to certain 
patients with malignant tumors and with cachexia. 46 Under 
these circumstances, it is naturally extremely difficult to main- 
tain a nitrogenous equilibrium. From what has been said, it 
will be seen that in the severer forms of diabetes malnutrition 
frequently develops ; for the patient is either unwilling or un- 
able to take a sufficient quantity of fats and proteids to cover 
his total needs, and, in addition, his consumption of proteid 
material is sometimes abnormally rapid. 

The metabolism in diabetic patients frequently shows other 
peculiarities as the disease becomes more advanced. Various 
organic acids, especially ,9-oxybutyric and diacetic acids are 
formed in the body. Indeed, they are produced in such quan- 
tities in no other condition as in some cases of diabetes melli- 
tus. We have already stated that when an excessive amount 
of acid is present in the body, it is neutralized by the ammonia 
which would otherwise have been converted into urea (p. 338). 
For this reason the excretion of organic acids in diabetes is 
associated with an increased elimination of ammonia in the 

45 Hirschfeld, Ztft. f. klin. Med., vol. xix. pp. 294, 325; Pautz, Ztft. 
f. Biol., vol. xxxii. p. 197. 

44 v. Mering, Kongr. f. in. Med., 1886, p. 188. 



364: CLINICAL PATHOLOGY 

urine. The source of the aceton and of the diacetic and 
/?-oxybutyric acids is of great theoretical and practical interest, 
for the resulting acidosis is apparently the most important cause 
of the dreaded diabetic coma (see p. 342). Unfortunately, 
however, the cause of the acidosis and the source of the acids 
is but little understood (see p. 342). 

In diabetes the nutrition of different parts of the body suf- 
fers in various ways. The crystalline lens of the eye may 
become opaque (diabetic cataract), and degenerations of the 
retina and choroid coat may develop. The arteries are often 
found to be sclerotic. (In some cases this is to be regarded 
as the cause rather than as the effect of the diabetes ; for it is 
associated with degenerative changes in the islands of Langer- 
hans. 4T — Ed.) 

Tissues that are permeated with sugar seem to offer an 
excellent medium for the growth of micro-organisms, and it 
is well known how frequently diabetics become infected and 
how often these infections terminate in gangrene. The dia- 
betic gangrene is due, in part, to the presence of excessive 
amounts of sugar in the tissue, and, in part, to the diminished 
blood-supply caused by an associated arteriosclerosis. 48 Pa- 
tients with diabetes are furthermore very susceptible to tuber- 
culosis, and here again the process shows a special tendency 
to develop into gangrene. Other complications, such as furun- 
culosis, caries of the teeth, gingivitis, and stomatitis, are also 
frequently present in diabetic patients (see p. 231). 

We know comparatively little concerning the relation that 
lesions of the kidneys bear to diabetes mellitus. Albuminuria 
is a not infrequent complication of the disease. In some cases 
it is due to a true nephritis, produced by the same cause which 
gave rise to the diabetes, such as arteriosclerosis, for example ; 
in other cases it is apparently quite an accidental complication. 

47 See Hoppe-Seyler, Arch. f. klin. Med., vol. lxxxi. p. 119. 

48 Konig, Berl. klin. Wochens., 1896, No. 25. 






DIABETES 365 

When the albuminuria develops late in the diabetes, it may 
be questioned whether the continuous passage of sugar through 
the kidneys has not directly harmed the secreting cells. In 
this connection we may recall the glycogenic degeneration of 
the kidney so often found in diabetes. 49 The immediate cause 
of this degeneration and its relation to albuminuria are, how- 
ever, insufficiently understood. That primary lesions of the 
kidney may cause glycosuria (renal diabetes) seems very prob- 
able (see p. 351). 

The amount of urine is often enormously increased in dia- 
betes, and as much as ten or fifteen litres may be passed in 
twenty-four hours. This is certainly dependent upon the ab- 
normal quantity of sugar in the blood; for if, by proper 
methods, the latter be diminished, then the amount of urine 
also diminishes. Conversely, the greatest diuresis occurs in 
the cases with the largest amounts of sugar in the urine. The 
accumulation of dextrose in the blood or in certain tissues seems 
to produce an intense thirst, and the water that is taken for 
this causes the increase in the amount of urine. Yet no very 
absolute definite relation exists between the amount of urine, 
the excretion of sugar, and the feeling of thirst, and it has 
been shown, for example, that even though the same quantities 
of sugar are being excreted daily, the quantity of urine may be 
different in different patients. 

Theory of Diabetes. — From the foregoing facts we shall 
now try to formulate a theory of diabetes mellitus. The sugar 
is excreted in the urine because of a hyperglycemia, an excess 
of sugar in the blood. One cause of this excess in the blood is 
that the liver has lost, to some extent, the property of storing 
tip the dextrose that comes to it either from the food or from 
the splitting up of proteids in the body. For those who believe 
that sugar can be formed in the body from proteids, the differ- 
ence between a severe and a mild type of diabetes consists in 
40 Fichtner, Arch. £. klin. Med., vol. xlv. p. 112. 



366 CLINICAL PATHOLOGY 

the ability or inability on the part of the liver to store up, and 
on the part of the body to consume, the carbohydrates derived 
from proteid sources. For those who deny that sugar is nor- 
mally formed out of proteids in the body, the essential feature 
of the severe form of diabetes is the formation of sugar in 
some abnormal manner from proteids. Pfliiger's extreme view- 
that sugar is never derived from proteids, unless these be glu- 
cosides, appears to me to be untenable; though it must be 
admitted that his views merit still further investigation. 

It is impossible to say to what extent the glycogenic func- 
tions of other organs, such as the muscles, are impaired in 
diabetes. It seems certain, however, that in some way the 
pancreas assists the liver and muscles in their glycogenic func- 
tion, and that this is one reason why lesions of the pancreas 
may lead to diabetes. 

In the milder cases of diabetes, it is possible that no other 
disturbances of function are present than the above-mentioned 
impairment of the glycogenic functions in the body. In the 
more severe forms of diabetes, however, there is undoubtedly 
a diminution in the ability of certain cells of the body, perhaps 
the muscle-cells, to assimiliate sugar. The pancreas seems to 
assist in the assimilation of sugar in the body, possibly by fur- 
nishing an internal secretion that activates the glycolytic fer- 
ments in the muscles. This action of the pancreas is perhaps 
similar to that of the enterokinase of the intestines which con- 
verts a protrypsin into a trypsin, or to the intermediary body 
that plays such an important part in haemolysis. 

The glycogenic function of the liver may certainly be influ- 
enced through the nervous system, as is proved by the effects 
of experimental puncture of the fourth ventricle, and it is quite 
possible that the nervous system serves in some way to connect 
the liver and the muscles. 50 This influence of the nervous 
system upon the glycogenic function of the liver, would explain 

60 Pfliiger, Pfliiger's Arch., vol. xcvi. p. I. 






DIABETES 367 

the etiological relation between nervous lesions and diabetes, 
a relationship that has been insisted upon by so many clinicians. 
Finally, one can hardly help thinking that a diabetes may 
be caused by lesions of different organs, especially of the liver, 
the pancreas, the muscles, etc. Perhaps it will ultimately be 
possible to distinguish different forms of the disease according 
to their origin, but at the present time, the most experienced 
investigators in this field regard diabetes mellitus as an indivisi- 
ble entity. 









CHAPTER IX. 

THE METABOLISM OF THE PURIN BODIES. GOUT. 

The nitrogen, derived from a certain class of proteids, the 
nucleo-proteids, is not excreted in the form of urea and am- 
monium salts to the same extent as is that derived from ordi- 
nary proteids. The characteristic constituents that enter into 
the composition of the nucleo-proteids are the nucleinic acids. 
When these undergo cleavage, they give rise to the purin or 
alloxuric bases, among which are adenine, guanine, xanthine, 
and hypoxanthine. A small portion of these bases appears in 
the urine as such, but the greater portion is eliminated in an 
oxidized form, as uric acid. 1 The uric acid and the purin 
bases are often spoken of together as the purin bodies. 

Most of the uric acid that appears in the urine is derived 
in this manner from nucleo-proteids that are broken down in 
the body, or from purin bases or related compounds, such as 
caffeine or theobromine, that are taken in the food. Not all of 
the uric acid, however, is derived from these sources, for it is 
now practically certain that this acid may be formed syntheti- 
cally in the human body, just as it is in the bodies of birds. 2 
Nor does all of the nitrogen contained in the nucleinic acids 
appear in the urine as uric acid or related compounds, for a 
certain proportion is converted into urea in the body. This 
latter fact gives some basis to the old conception that uric acid 
represents an early stage in the formation of urea. 

The quantity of purin bases in the urine serves therefore 

1 Kossel, Ztft. f. physiol. Chem., vol. iii. p. 284; vol. vi. p. 422; Min- 
kowski, Arch. f. exp. Path., vol. xxi. p 86; Horbaczewski, Monatsch. f. 
Chem., vol. xii. p. 221. 

2 See Wiener, Asher-Spiro, Ergebnisse, vol. i. p. 555; vol. ii. p. 377; 
Schmoll, Johns Hopkins Hosp. Bull., vol. xv. p. 377. 

368 



GOUT 369 

as a rough index of the bodily consumption of nucleo-proteids 
and purin bodies, derived either from the cellular metabolism 
or directly from the food. 3 Yet, as we have seen, it cannot 
serve as an accurate and absolute index of such consumption; 
for, on the one hand, not all of the nitrogen in the nucleinic 
acid appears in the urine as purin bodies, and, on the other 
hand, these bodies may be formed synthetically within the living 
organism. 

Cell nuclei are very rich in nucleo-proteids; and when the 
food taken contains many nuclei, as is the case with thymus 
gland, for example, then the amount of purin bodies in the 
urine is greatly increased. Conversely, if a person avoids those 
substances which can be readily converted into purin bodies, 
such as the nucleo-proteids of meats and seeds, the caffeine of 
coffee, etc., then the quantity of uric acid in the urine is dimin- 
ished, and that which does appear there represents the amount 
actually formed within the body. The amount of this " en- 
dogenous" uric acid has been found to be different in different 
individuals, though it is fairly constant for the same individual 
at different times. 4 It is apparently somewhat influenced by 
the ingestion of large quantities of non-nitrogenous food. 5 

The elimination of endogenous uric acid is increased when- 
ever large numbers of cells, rich in nucleo-proteids, are being- 
destroyed in the body. This was early demonstrated for a 
particular kind of cells, the leucocytes; and this fact, among 
others, led Horbaczewski to the belief that the leucocytes are 
a specific source for purin bodies, a view now proved to be 
incorrect. 8 Leucocytoses are, however, frequently accompanied 

' Camerer, Ztft. f. Biol., vol. xxxv. p. 206; Weintraud, Kongr. f. in. 

Med., 1S98, p. 190. 

1 I'urian and Schnr, Pfliigcr's Arch., vol. lxxx. p. 241 ; vol. lxxxvii. 
P- 239. 

'Kanfmann and Mohr, Arch. f. klin. Med., vol. lxxiv. p. 141. 

6 See Hoffmann, Konstitutionskr. ; Ebstein, Kongr. f. in. Med., 1889, 
P- 143. 

24 



370 CLINICAL PATHOLOGY 

by an increased elimination of purin bodies, and when this is 
so, we may assume that an abnormal destruction of leucocytes 
is taking place in the body. Very large amounts of uric acid 
are often excreted in leukaemia, especially in the acute form 
of the disease. 7 In the chronic cases of this disease, the elimi- 
nation of uric acid is usually increased, though in some no 
such increase in uric acid has been found. 8 Too little attention 
has been paid, however, to the excretion of the purin bases in 
these cases, for it has been shown that though the uric acid be 
normal, the purin bases, and consequently the total purin 
bodies, may be increased. 9 

The urine of the new-born child contains remarkably large 
quantities of uric acid. These are found at about the same 
time that uric acid infarcts are most liable to occur in the 
kidneys. The meaning of this increased elimination, however, 
is not yet fully understood. 10 

Gout. — Gout is characterized by the deposition of mono- 
sodium urate crystals in various parts of the body, especially 
in the hyaline and fibrous cartilages, in the tendons, in the sub- 
cutaneous and intermuscular connective tissues, and in the 
kidneys. These deposits take the form of clusters of needle- 
like crystals. No symptoms may be caused by such a depo- 
sition of urates, especially when it takes place gradually and 
in certain localities, as the subcutaneous tissues and some car- 
tilages. These urate deposits, known as tophi, often attain a 
large size, and they may then break through the skin or again 
disappear without having caused any unpleasant sensations. 
In these cases it seems improbable that the uric acid should 
have been formed locally by the cells, for the strands of con- 



7 Magnus-Levy, Virch. Arch., vol. clii. p. 107. 

8 Gumprecht, Ztrbl. f. Path. vol. vii. p. 824. 

9 Gottlieb and Bondzynski, Arch. f. exp. Path., vol. xxxvi. p. 127: 
Gumprecht, loc. cit. 

10 Sjoquist, cit. Jahresber. f. Thierche, vol. xxiii. p. 245. 



GOUT 371 

nective tissue are pushed aside, and the tophi increase in size 
by new deposits on their exteriors. 

On the other hand, the deposition of urates in the tissues 
may lead to a more or less marked inflammatory reaction in 
the neighborhood, and this may be accompanied by the char- 
acteristic paroxysm of acute gout. Suddenly or after some 
prodromal symptoms, the patient is awakened at night by 
violent pains in one or more joints, usually in the metatarso- 
phalangeal joints of the great toes. The affected joint and 
the neighboring tissues become intensely inflamed, and the skin 
over them becomes cedematous. These very acute symptoms 
usually do not last long, and after a few hours or days they all 
disappear without necessarily leaving any alterations in the 
joint that can be demonstrated even by anatomical methods. 
These typical acute gouty paroysms may recur at varying inter- 
vals; but gradually they become less and less characteristic, 
the patient becomes cachectic, and the " regular gout" is said 
to have become transformed into the asthenic form of the 
disease. 

The exact cause of these typical paroxysms is uncertain. 
According to one view, the inflammation is caused by the depo- 
sition of uric acid or some of its derivatives in the tissues. At 
present, however, this is a pure hypothesis, unsupported by 
facts, and it encounters the great objection that tophi are fre- 
quently formed without any symptoms whatever. According 
to another view, the paroxysms are caused by a too rapid 
solution of urates from old deposits, yet this view likewise 
lacks the support of direct evidence. In truth, no satisfactory 
explanation of the gouty paroxysms can be given, and we are 
equally ignorant concerning the nature of many associated 
gouty manifestations, such as the granular kidney and the 
heart changes, the pulmonary, nervous, and ocular complica- 
tions and the general cachexia. 

it is said that a tendency to gout may be inherited, and that 



372 CLINICAL PATHOLOGY 

the disease may be caused by excesses in food and drink. We 
consider, however, that caution is necessary in the acceptance 
of these views, for they rest not upon convincing statistics, but 
rather upon so-called clinical experience and impressions. 
More accurate data on this subject are therefore very desirable. 
That chronic lead poisoning favors the development of gout 
can hardly be doubted, 11 though how it does so is quite uncer- 
tain. The nature of the relation between gout and diabetes 
mellitus and between gout and obesity are likewise unsolved. 

Uric Acid in the Blood during Gout. — During the gouty 
paroxysm, uric acid crystallizes out of the blood with abnormal 
ease after the addition of acetic acid. 12 It crystallizes out of 
normal blood in a similar manner only when a large amount 
of nuclein compounds have been taken in the food. In patho- 
logical conditions other than gout, especially in leukaemia, 
however, large quantities of uric acid will at times crystallize 
out of the blood just as it does in acute gout. 13 In the intervals 
between the gouty paroxysms no such excess of uric acid in 
the blood can be demonstrated. 

It is impossible to explain the ease with which uric acid 
precipitates out of gouty blood, so long as we do not know 
how it is held in solution in normal blood. 14 To dissolve one 
part of uric acid about thirty-eight thousand parts of pure 
water are necessary, 15 yet serum will dissolve uric acid at the 
body temperature up to a concentration of about 0.18 per 



"Liithje, Ztft. f. klin. Med., vol. xxix. p. 266. 

12 Garrod, The Nature and Treatment of Gout ; Klemperer, Deut. med. 
Wochens., 1895, No. 40; Magnus-Levy, Ztft. f. klin. Med., vol. xxxvi. 
p. 366. 

13 Magnus-Levy, Virch. Arch., vol. clii. p. 107 ; Ztft. f. klin. Med., vol. 
xxxvi. p. 372. 

14 See Minkowski, Gicht in the Nothnagel System ; G. Klemperer, 
Kongr. f. in. Med., 1902, p. 219; Goto, Ztft. f. physiol. Chem., vol. xxx. 
P- 473- 

10 His and Paul, Ztft. f. physiol. Chem., vol. xxxi. pp. 1 and 64. 



GOUT 373 

cent. 16 Minkowski has called attention to the fact that too 
great stress is ordinarily laid upon the alkali of the blood as a 
solvent for uric acid, and too little attention has been paid to 
the possibility that the acid is held in solution in some other 
combination, such as one with nucleinic acid. 

The increased amount of uric acid in the blood of gouty 
patients can hardly be regarded as the sole cause of the pre- 
cipitation of the mono-urate in the tissues, for the blood con- 
tains excessive amounts of uric acid in other conditions, such 
as leukaemia, for example. Furthermore, there is no reason 
to suppose that the blood of gouty patients cannot dissolve as 
much acid as does the blood of normal individuals. At least, 
no diminution in the alkalinity of the blood can be demon- 
strated, either by determinations of the carbon dioxide dis- 
solved or by direct titrations. 17 Klemperer has shown, indeed, 
that the blood of these patients is still capable of dissolving 
even considerable amounts of uric acid. 

The Uric Acid in the Urine in Gout. — Previous to the 
gouty paroxysms, there is a diminished excretion of uric acid 
in the urine; whereas, during and just after the paroxysm, 
more is excreted than at other times. 18 The excretion of the 
purin bases is also said to be increased along with the increase 
in uric acid. If food rich in nuclein compounds — e.g., thymus 
— be taken during the paroxysm, the uric acid is not excreted 
so well as it is by a normal individual. 19 

In chronic gout, and during the intervals between the parox- 
ysms of acute gout, no definite abnormalities in the excretion 
of uric acid can be demonstrated, 20 although Soetbeer believes 

10 G. Klemperer, Deut. mcd. Wochens., 1895, No. 40. 

17 Magnus-Levy, Ztft. f. klin. Med., vol. xxxvi. p. 376. 

18 His, Arch. f. klin. Med., vol. Ixv. p. 156; Magnus-Levy, Ztft. f. 
klin. Med., vol. xxxvi. p. 380. 

"Vogt, Arch. f. klin. Med., vol. Ixxi. p. 21; Soetbeer, Ztft. f. 
physiol. Chem., vol. xl. p. 25. 

M His, Arch. f. klin. Med., vol. Ixv. p. 156. 



374 CLINICAL PATHOLOGY 

that after the administration of meat the excretion of uric acid 
did not follow precisely the normal course, and in some cases 
it was quantitatively diminished or delayed. 21 

One might be inclined to attribute the increase of uric acid 
in gouty blood to an insufficient excretion of urates by the kid- 
neys, and this supposition receives some support from the fact 
that other nitrogenous waste products may also be retained in 
the body, both in the acute paroxysms and in chronic gout. 22 
No anatomical grounds for such a retention are, however, 
demonstrable, for the gouty granular kidney is usually only a 
late manifestation of the disease. 

The retention of uric acid in gout may not be due to renal 
changes at all, and Minkowski's idea that this substance circu- 
lates in a form which is not readily excreted is deserving of 
careful investigation. That some such relation may exist is 
supported by the fact that a retention of ammonium and potas- 
sium salts has been observed during the gouty paroxysm. 23 

The Cause of the Local Deposits of Urates. — According 
to many of the best observers, 24 the local deposit of the urates 
in gout is caused by changes in the cells of the affected regions. 
This seems to be true in the primary attacks at least. As has 
been mentioned, however, there is less reason to believe that 
the more chronic deposits in the subcutaneous tissues, etc., are 
caused by primary cellular changes. Ebstein has laid great 
weight upon a primary necrosis of the tissue as the cause of 
the precipitation of urates, but later researches have not sup- 
ported his views. 25 

21 Ztft. f. physiol. Chem., vol. xl. pp. 25, 55. 

^Vogel, Ztft. u. klin. Med., vol. xxiv. p. 512; Schmoll, Ztft. f. klin. 
Med., vol. xxix. p. 510; Magnus-Levy, Ztft. f. klin. Med., vol. xxxvi. 
p. 380; Vogt, Arch. f. klin. Med., vol. lxxi. p. 21. 

23 Soetbeer, Ztft. f. phys. Chem., vol. xl. p. 55. 

24 Klemperer, Horbaczewski, v. Noorden. 

25 Freudweiler and His, Arch. f. klin. Med., vol. Ixiii. p. 266; His, 
ibid., vol. lxvii. p. 81. 



GOUT 



375 



Theory of Gout. — It must be admitted that, in the present 
state of our knowledge, no adequate theory to explain gout 
has been advanced and that we hardly know more than that 
it is associated in some way with a perversion of the uric acid 
metabolism. To attain to a more satisfactory knowledge of 
this subject, it will be necessary to arrive at some more definite 
understanding as to the relation which exists between the for- 
mation and the excretion of uric acid under normal as well as 
pathological conditions, to obtain more accurate data as to the 
amount of uric acid contained in the tissues and fluids of the 
body, and, finally, to know the form in which uric acid is nor- 
mally held in solution. The latter is, perhaps, of primary 
importance, and definite disturbances in the solubility of the 
uric acid would explain many facts connected with gout. 






CHAPTER X. 



Fever is characterized by an increase in the temperature 
of the body and by certain changes in the metabolic processes. 1 
The temperature in fever is higher than is normal for the time 
of day at which it is taken. The temperature is furthermore 
much less constant than is the normal temperature, and the 
considerable variations that it undergoes are due partly to 
external influences and are partly spontaneous, or, at least, 
due to causes which escape our methods of observation. 

As a rule, the diurnal variations of the temperature in fever 
are of the same character as those which take place in health, — 
i.e., there is an elevation toward evening and a fall toward 
morning. Those who work at night and sleep during the day 
show at times the inverse type of diurnal variation both in 
health and fever. Thus we see that the same causes, such as 
food, light, work, etc., which influence the temperature curve 
of healthy persons, also influence the variations in the tempera- 
ture of fever patients. In many fevers, however, the variations 
in temperature are quite irregular, or they follow some special 
type that is characteristic of the disease. 

The rise of temperature is only one of a number of phe- 
nomena which are present in fever, and it is often difficult to 
decide whether many of the other symptoms are to be ascribed 
to the high temperature or are due directly to the agent that 
causes the fever. We only are justified in regarding a par- 
ticular symptom as a result of the increased temperature when 
it is found to occur in all forms of fever, no matter how they 
are caused. 

1 See Krehl, Kongr. f. in. Med., 1898, p. 229. 
376 



FEVER 377 

The Normal Regulation of the Body Temperature. — The 
temperature of man is maintained at an almost constant level 
under the most varying conditions ; indeed, it varies less than 
that of any other animal. We shall therefore first consider 
the mechanism by which the temperature is normally main- 
tained at this uniform level. 2 

If large quantities of heat are suddenly set free in the body 
from any cause, such as muscular work or the ingestion of large 
amounts of food, then the total loss of heat from the body is 
correspondingly increased. The cutaneous vessels dilate and 
the warmer skin loses heat more rapidly by radiation and con- 
duction. The affected person perspires more freely, and the 
loss of heat by evaporation of water from the skin is likewise 
increased. Whether the one or the other of these various 
means for eliminating heat is utilized to a greater or less extent 
in the individual case depends upon a variety of conditions, 
which cannot be considered in this place. 

If, on the other hand, a warm-blooded animal is exposed 
to cold, it is able to protect itself from considerable losses of 
heat, which would otherwise tend to reduce its temperatures. 
The skin vessels contract and the heat losses through con- 
duction and radiation are diminished. Men ordinarily wear 
thicker clothes under these circumstances, and so surround 
their bodies with a layer of comparatively warm air. By these 
means it is possible to maintain the normal bodily temperature, 
even when the individual is exposed to considerable degrees 
of cold. If, however, this mechanism is insufficient to meet 
the emergency, then a new factor is called into play. The 
production of heat in the body is increased, the seat of this 
increased production being the muscles, according to the best 
authorities. 

When a man is exposed to cold, therefore, the first. regu- 

2 Sec Rubner 1 da ical work, Die Gcsetzc des Energieverbrauchs bei 
der Ernahrung, Leipzig, 1902. 



378 CLINICAL PATHOLOGY 

latory mechanism that serves to maintain his body temperature 
at the normal level is of a physical character; i.e., losses of 
heat are prevented. As we have just seen, however, this 
means of regulation may be insufficient, and the exposure to 
cold is then followed by an increased production of heat in the 
body. The individual feels chilly and shivers, and thereby in- 
creases the combustion in his body, and, even though no gross 
muscular movements occur, the body metabolism may yet be 
increased, as has been proved by recent experiments. In such 
a case the extra heat is generated mainly by the combustion of 
non-nitrogenous material, just as it is when heat originates 
from muscular activity. This regulation of the body tem- 
perature by variations in the heat production is termed a 
chemical regulation in contradistinction to that which depends 
upon variations in the heat losses, the so-called physical regu- 
lation. 

The point at which the chemical mechanism steps in to 
maintain the temperature of the body depends in part upon 
the degree to which the animal is able to limit his loss of heat 
and in part upon the amount of food which has been taken. 
The heat that is immediately set free when food is taken would 
ordinarily be quickly disposed of by an increased elimination 
of heat; but if the body is exposed to cold, this extra heat 
serves to maintain the body temperature. It thus obviates the 
necessity of calling the chemical regulation into play. 

These are, in brief, the means whereby the healthy man 
regulates his bodily temperature under varying external and 
internal conditions. Under certain circumstances, however, 
even the normal mechanism is insufficient to keep the body at 
a constant temperature. For example, if heat be applied to 
the surface of the body, and if, at the same time, the compen- 
satory loss of heat be interfered with, then a rise in temperature 
necessarily follows. For this reason, every man becomes 
warmer in a steam bath, or in a warm-water bath of 40 C. 



FEVER 379 

(104 F.) or over. Possibly, however, some become warmer 
than others under the same conditions. 

An increased production of heat within the body by exces- 
sive chemical decomposition may also cause a rise in tempera- 
ture, and this happens more frequently than is generally 
supposed. 3 Muscular exertion, even if not very severe, may 
thus raise the temperature of the body. In this respect, dif- 
ferent individuals certainly react differently, and the novice 
becomes overheated in doing a certain piece of work more 
easily than does the adept, mainly because he uses more energy 
to accomplish the same result. Another factor that is of great 
importance here is the ease with which heat may be eliminated 
from the body. This explains many of the apparent contra- 
dictions met with in literature concerning the effect of muscular 
exertion upon the body temperature. The man that makes 
the ascent of Monte Rosa does not become warmer from the 
great exertion, because the low temperature and the dryness 
of the surrounding air greatly favor the loss of heat from his 
skin and lungs. 4 On the other hand, the temperatures of sol- 
diers frequently rise during forced marches, for they are 
heavily dressed and they must often travel in a warm, moist 
climate. 

Heat Stroke. — If the temperature of the body becomes 
considerably elevated from such outside causes, we speak of 
it as a heat stroke. 5 The temperature under these conditions 
may reach 43 ° C. (no° F.) or over, the pulse becomes rapid, 
the patient becomes dizzy or delirious, and in severe cases coma 
and death terminate the scene. The high temperature often 
persists in these patients for hours, or even days, after the 

* Hiller, Ztft. f. klin. Med., vol. xxiii. p. 399; Wolpert, Arch. f. Hyg., 
vol. xxvi. p. 32. 

* Calberla, Arch. f. Heilkundc, vol. xvi. p. 276; Bonnal, Comptes 
rendus, vol. xci. p. 798. 

"Zuntz, Bcrl. klin. Wochcns., 1896, No. 32. 



380 CLINICAL PATHOLOGY 

actual cause of the stroke is over. This would seem to indicate 
some injury to the heat-regulatory mechanism. Heat-stroke 
patients are often described as being pale, livid, or cyanotic, 
which conditions indicate an improper peripheral circulation 
and a consequent improper regulation of the heat losses from 
the surface of the body This poor peripheral circulation is 
apparently due to an injury to the regulating centres in the 
brain, though the nature of this injury is not known. 

The experience of military surgeons has taught us that ex- 
cessive heat is most liable to affect those who are in some way 
indisposed, who are foot-sore, or who are convalescent from 
severe illness, and it has frequently been observed clinically 
that persons who are ill, particularly anaemic or tuberculous 
patients, are especially prone to show a rise of temperature 
after exercise, or even after meals. 6 

It may be questioned whether the rise of temperature pro- 
duced by such external agencies should be regarded as fever 
or not. One might say that the heat regulation is sufficient 
under ordinary circumstances, but insufficient when special 
demands are made upon it Such a distinction is merely one 
of degree, and the comparison could then be made with the 
heart which is sufficient so long as the body is at rest, but 
becomes insufficient when increased work is demanded of it. 

It were perhaps better to attempt to draw a line dividing 
those cases in which regulatory mechanism is affected, as it is 
known to be in fever, from those in which the regulatory 
mechanism is normal, but cannot reduce the temperature 
owing to the nature of the conditions that surround the body. 

In heat stroke the conditions are very complicated, and the 
rise of temperature is not due to external forces alone. Other 
factors, in addition, are certainly present, for different indi- 

6 Penzoldt and Birgelen, Munch, med. Wochens., 1899, Nos. 15, 16, 17; 
Ott, ibid., 1901, No. 50, and 1902, No. 38; Schroder and Briihl, ibid., 
Nos. 33, 34, and 45. 



FEVER 381 

viduals show considerable differences in their susceptibility 
to changes in their environment. Some lose heat more readily 
than others, a fact that is especially true of thin individuals 
as compared with stout ones. Heart lesions render a patient 
very susceptible to heat stroke, for a good peripheral circula- 
tion is a necessity when the losses of the heat from the body 
must be increased. 7 (An overindulgence in alcohol also ren- 
ders an individual more susceptible to heat stroke. Finally, 
those who have had once a sun stroke may manifest for years 
a markedly increased susceptibility to changes in the tempera- 
ture about them. — Ed.) All these facts demonstrate that 
changes in the external conditions are not the sole factors 
which produce the sun stroke. The mechanism for losing heat 
is certainly less efficient in some individuals than in others, 
and in so far as the heat stroke depends upon an insufficiency 
of heat elimination it bears a certain resemblance to true fever. 

Heat Regulation in Fever. — The cause of the high tem- 
perature of fever must be some disproportion between the 
production and the loss of heat in the body. Theoretically, 
fever might be caused either by an excessive heat production 
without a corresponding increase in the heat loss, or by a 
diminution in the heat loss without a corresponding diminution 
in the heat production. We now propose to consider which 
of these conditions actually exists in fever, and whether or 
not all cases of fever are produced in the same manner. 

Two general methods have been employed to determine 
the amount of heat produced in the body. In the first, the 
amount of heat lost has been directly measured in a calorimeter 
(direct calorimetry). In the second, the products of com- 
bustion have been determined and the beat produced calcu- 
lated (indirect calorimetry). The two methods have been 
shown to yield identical results in the healthy animal. B and 

7 Tliiirn. Deut militararztl. Ztft, [895, p. 289. 

8 Rubncr, Ztft. f. Biol. N. F., vol. xii. p. 73- 



382 CLINICAL PATHOLOGY 

we have every reason to believe that the results would also 
be the same in fever, although this has not yet been definitely 
proved, on account of technical difficulties. 9 

Heat Production in Fever. — In the vast majority of all 
fevers the production of heat is increased. This has been 
proved for different diseases of man, such as pneumonia, 
typhoid fever, pleurisy, erysipelas, tuberculin fever, etc., 10 as 
well as for various septic diseases of animals, 11 and for fevers 
produced experimentally by injections of bacteria and various 
chemical substances. 12 

This increase in heat production is quite marked at the 
time when the temperature is rising and at the height of the 
fever. It is greatest of all during the chill which initiates so 
many infections, obviously on account of the violent muscular 
contractions that take place at that time. During the height 
of the fever, it is found to be the most marked in those who 
breathe violently, from whatever cause; here also because of 
the excessive muscular exertion. If we eliminate these cases, 
in which the heat production is accelerated by muscular activity, 
then the increased production of heat in fever usually amounts 
to from ten to sixty per cent., the average being about twenty 
to thirty per cent. 

In a small number of cases no apparent increase of heat 
production above the normal limits can be demonstrated. 13 
Such observations have been made, for the most part, upon 
patients in whom there was but little fever or in whom the 

9 See Krehl and Matthes, Arch. f. exp. Path., vol. xxxvii. p. 284. 

10 Leyden, Arch. f. klin. med., vol. vii. p. 536; Liebermeister, ibid., 
vol. viii. p. 153; Loewy, Virch. Arch., vol. cxxvi. p. 218; Riethus, Arch. 
f. exp. Path., vol. xliv. p. 239. 

11 Leyden and Fraenkel, Virch. Arch., vol. lxxvi. p. 136. 

12 Krehl and Matthes, Arch. f. exp. Path., vol. xxxviii. p. 284. 

13 F. Kraus, Ztft. f. klin. Med., vol. xviii. p. 160 ; Kraus and Chvostek, 
Wiener klin. Wochens., 1891, Nos. 6 and 7; Loewy, Virch. Arch., vol. 
cxxvi. p. 218; Krehl and Matthes, Arch. f. exp. Path., vol. xxxviii. p. 284. 



FEVER 383 

fever was long continued. In the latter class of cases it is 
necessary to remember that the organism tends to limit its 
metabolism in long-continued illnesses, so that although the 
quantity of oxygen consumed by these patients with fever 
may not have exceeded the normal limits, it was in reality 
above what would have been consumed had no fever been 
present. For accurate comparisons in such cases, comparative 
determinations should be made upon the same individual dur- 
ing periods of fever and of apyrexia. 

In still another class of cases high fever may be associated 
with an unusually low production of heat — viz., when there 
is a tendency to collapse. As we shall see later, a diminution 
in the heat production is one of the characteristics of collapse, 
and even when a tendency to this condition is present the heat 
production may be lessened. 

In a final group of cases no reason can be given for the 
slight production of heat, and in these it is possible that the 
sole cause of the rise of temperature is a limitation of the heat 
losses from the body. 14 

Thus we see that in the great majority of all cases of 
fever, and especially in fevers of short duration, the produc- 
tion of heat in the body is increased. This increase is most 
marked at the beginning of acute infectious diseases, whereas, 
in chronic wasting diseases the heat production tends to be- 
come limited, and when the temperature is falling it may even 
be less than normal. 

As we have said, the average increase in the heat pro- 
duction in fever is about 20 to 30 per cent. Such an increase 
is not extraordinary when we remember that Rubner was 
able to increase the heat production in dogs sixty per cent, 
solely by feeding them with large quantities of proteid food, 
and that in severe muscular exertion the heat production may 
be several times as great as during rest. Normally, the body 
" Rosenthal, Bcrl. klin. Wochcns., 1891, No. 32. 



384 CLINICAL PATHOLOGY 

can dispose of much larger amounts of heat than are liberated 
within it during fever, so that the cause of the high tempera- 
ture in fever cannot be an increased production of heat alone. 

Indeed, a portion of the increase in heat production is due 
to the elevation of the body temperature itself, for we know 
that oxidative processes in general are accelerated by heat, 
and Pfliiger has estimated that for every increase of i° C. 
in a rabbit's temperature, its heat production increases about 
six per cent., and the same has been shown to be true when 
the temperature of man is artificially elevated. 15 Thus we 
see that an increase of heat production, amounting to about 
twelve to eighteen per cent, of the normal, might easily be 
explained as an effect rather than as a cause of the increased 
bodily temperature. The excessive heat production in fever, 
therefore, may be explained in part as a result of increased 
muscular movements and in part as the result of the higher 
temperature of the body. The remaining increase in heat pro- 
duction is very slight ; especially if it be compared to that 
which results from violent exercise or from the ingestion of 
large quantities of proteid food. 

The Loss of Heat at the Beginning of Fever. — During 
the rise of temperature the loss of heat from the body is almost 
always found to be diminished, the losses by radiation and 
conduction from the skin being especially limited. The amount 
lost by evaporation of water is frequently increased, however ; 
for, even at this period, the metabolic processes in the body 
may be accelerated. Yet the increased loss by evaporation 
does not neutralize the decrease in loss by conduction and 
radiation, and frequently, furthermore, the loss of water is 
also less than normal. Thus at the onset of fever the animal 
utilizes all of the means at its disposal to raise its temperature. 
The production of heat is increased and the losses are dimin- 
ished. 

"Linser and Schmidt, Arch. f. klin. Med., vol. lxxix. p. 514. 



FEVER 385 

The loss of heat from the surface of the body is regulated 
mainly by the contraction of the cutaneous blood-vessels. At 
the onset of many diseases these vessels contract excessively, 
and, as a consequence, the skin becomes cold and either pale or 
cyanotic. This cooling of the skin produces in turn a sensa- 
tion of cold throughout the body and sets in motion the chemi- 
cal mechanism already referred to (p. 378), which increases 
the heat production within the body. Clonic muscular move- 
ments, giving rise to the so-called chill, are a consequence. 
During the chill, the temperature rises rapidly to a great height, 
for the muscular movements greatly increase the heat pro- 
duction, and, at the same time, the heat losses are reduced 
on account of the contracted cutaneous arteries. That these 
muscular contractions are due primarily to the coolness of the 
skin is proved by the fact that, if the skin of these patients 
be warmed, the " chill" ceases. Such chills are particularly 
characteristic of some diseases, and it seems probable that the 
agents which cause certain fevers show a special tendency to 
produce a constriction of the cutaneous vessels, and conse- 
quently a chill. 

The Heat Loss at the Height of the Fever. — In the great 
majority of cases the total loss of heat is increased at the 
height of the fever. This is necessarily true when the heat 
production is increased and the temperature is constant, for 
it is obvious that, if the extra heat produced were not imme- 
diately given off, the temperature of the body would be raised. 

In animals the acceleration in heat losses affects conduction, 
radiation, and evaporation, all to about the same degree; so 
that the ratio between the first two and the third remains prac- 
tically the same as in health, — i.e., the loss by the evaporation 
amounts to about sixteen to seventeen per cent, of the total 
loss of heat. 10 In my opinion, however, we are not permitted 

"Nebclthau, Ztft. f. Biol., vol. xxxi. p. 293; Krchl and Matthes, 
Arch. f. exp. Path., vol. xxxviii. p. 284. 

25 



386 CLINICAL PATHOLOGY 

to infer from this that sufficient evaporation from the body 
takes place in fever, for it has been shown that, if the heat 
production be increased by other means, the losses by evapora- 
tion are relatively much more increased than are the losses by 
radiation and conduction. 17 

Lang has studied these relations in man. 18 In his ex- 
periments he showed that the ingestion of food greatly in- 
creased the evaporation of water from the bodies of both 
healthy and feverish patients; and that, on the other hand, 
if the patient were fasting, the evaporation from the skin 
during the rise of fever was less than the normal, and during 
the height of the fever it was approximately the same as nor- 
mal. The loss of water by way of the lungs, however, was 
considerably increased, owing to the larger amount of air 
breathed. His results, therefore, would seem to indicate that 
although the excessive heat derived from food will increase 
the evaporation from the skin even in fever patients, the ex- 
cessive heat caused by the fever itself does not tend to increase 
this evaporation. As yet, however, we cannot regard the ques- 
tion concerning the loss of heat by evaporation during fever 
as being definitely settled, for Lang's experiments were only of 
short duration. Nevertheless, it seems very probable that the 
cause of the rise of temperature in fever is, in part at least, an 
insufficient evaporation of water from the skin. 19 

Though the total heat loss during the height of the fever 
is ordinarily greater than normal, it is probably not so in those 
chronic cases already referred to, in which the heat production 
is normal or even diminished (p. 382) ; for, as we have said, 
so long as the temperature of the body remains constant, the 
total heat loss must equal the total heat production. It is only 

17 Rubner, Arch. f. Hyg., vol. xi. p. 256 ; Wolpert, ibid., vol. xxvi. 
pp. 32, 68; Zuntz, Berl. klin. Wochens., 1896, No. 32. 

18 Arch. f. klin. Med., vol. lxxix. p. 343. 

19 See also Leyden, Arch. f. klin. Med., vol. v. p. 273. 



FEVER 387 

during a rise or fall in the body temperature that the one 
exceeds the other. 

The conduction and radiation of heat from the skin are 
mainly governed by the amount of blood that traverses the 
cutaneous capilaries, and, since the latter are usually dilated at 
the height of the fever, the skin is ordinarily reddened at this 
time. Yet many questions concerning the cutaneous vessels 
in fever are still unsolved. They certainly respond excessively 
to stimulation, either mechanical or thermic, and, for this 
reason, fever patients easily become chilled when exposed to a 
draught of air, etc. Animals with fever also react excessively 
to reflexes which affect the cutaneous vessels through the 
medulla. 20 

Many have held that the cutaneous vessels of fever patients 
are subject to frequent and rapid variations in their state of 
contraction. This is certainly not always so, however, for, 
though recent and careful observations on animals have shown 
that during the rise of temperature considerable variations in 
the heat loss may take place, the same is by no means true 
during the height of the fever. 21 Furthermore, there are no 
very marked variations in the skin temperature of man during 
typhoid fever, rheumatic endocarditis, and many other con- 
ditions. 22 

Despite our inadequate knowledge on many of these points, 
we may say in conclusion that the temperature remains elevated 
during the height of fever, mainly because the mechanism 
regulating heat loss is ineffectual, and especially because the 
evaporation of water from the skin is insufficient. It seems 
as if the manner in which heat is produced during fever does 
not furnish an adequate stimulus to the mechanism that in- 
creases the loss of heat from the body, for if the heat pro- 

20 Heidenhain, Pfliiger's Arch., vol. iii. p. 504, vol. v. p. 106. 

21 Nebelthau, loc. cit. ; Krehl and Matthes, loc. cit. 

■ Griinenwald, Arch. f. klin. Med., vol. lxxviii. p. 333. 



388 CLINICAL PATHOLOGY 

duction of fever patients be increased in some other manner, 
as by the taking of food, for example, the extra heat thus 
produced increases the heat elimination. 23 

The Heat Loss during the Fall of Temperature. — This 
differs under different conditions. When the fall of tempera- 
ture takes place rapidly by crisis, the loss of heat is greatly 
increased by the sweating and by the increased radiation and 
conduction from the skin. When the fall of temperature takes 
place very gradually, however, the heat loss is often very slight. 
In such cases the fall is due mainly to a diminished heat pro- 
duction, as has been definitely proved for animals, and as is 
probably equally true of man. In the majority of cases, how- 
ever, the fall of temperature seems to be due to a combination 
of diminished heat production and increased heat loss. 

Quantitative Metabolic Changes during Fever. — During 
the rise of temperature, as well as during the height of fever, 
the oxidative processes in the body are usually increased. They 
run parallel to the heat production, and, indeed, may be used 
to measure heat production (indirect calorimetry), providing 
that we know what compounds are being oxidized and what 
the end products are. Chills and rapid respirations — i.e., mus- 
cular activity — greatly accelerate the metabolism, and a high 
temperature will do the same. In some cases of fever, how- 
ever, there is no apparent increase in the metabolic process 
(p. 382). No strict parallelism exists between the rate of 
decomposition and the elevation of temperature, 24 and many 
infections run their course with comparatively slight fever and 
yet with comparatively rapid rates of oxidation. 

The Proteid Metabolism during Fever. — Since most fever 
patients are placed upon an insufficient diet, their metabolism 
must be compared with that of healthy individuals who are on 
an equally low diet. It has been shown that during fever 

23 Lang, Arch. f. klin. Med., vol. lxxix. p. 343. 

" 4 See Riethus, Arch. f. exp. Path., vol. xliv. p. 247. 



FEVER 389 

there is an increased consumption of proteid material, both 
in men 25 and in animals, 26 though some few observers have 
failed to confirm these findings. 27 In many cases the increased 
proteid destruction begins even before the rise of temperature, 28 
and when the temperature falls rapidly, the increased elimina- 
tion of nitrogenous waste products frequently continues for 
some days after the temperature has become normal (the " epi- 
critical excretion of urea"). 29 Fever is, therefore, one of the 
conditions that injure the proteids of the body and increase 
nitrogenous metabolism. 

The rapidity of proteid decomposition varies greatly in 
different infections and in different individuals. It is most 
rapid in acute processes and in young, strong persons, and it 
is often comparatively slow in chronic wasting diseases. It 
bears no definite fixed ratio to the degree of temperature. 

The proteid decomposition in fever follows other lines 
than are followed during health, whether the individual is 
fasting or not. The significance of the appearance of aceton 
bodies in the urine need not be discussed here, for they are 
caused, in part at least, by the inanition, and it is questionable 
whether they are derived from the decomposition of proteids 
or of fats. It is certain, however, that a hydration of the 
proteid molecules occurs in fever, for albumoses mostly of the 
deutero group, have been found very frequently in the urine. 30 
To what extent this cleavage of the proteids is characteristic 
of fever will be discussed in another place (p. 390). 

Most of the end products of proteid decomposition that 

20 See v. Noorden, Path. d. Stoffwechsels, p. 193. 

24 Krehl and Matthes, Arch. f. exp. Path., vol. xl. p. 396. 

27 Pipping, Skandinav. Arch. f. physiol., vol. ii. p. 89. 

28 Ringer, Trans, of the Med. and Chir. Society, vol. xlii. p. 361 ; May, 
Ztft. f. Biol., vol. xxx. p. 1. 

29 Naunyn, Arch. f. exp. Path., vol. xviii. p. 49. 

30 Schultess, Arch. f. klin. Med., vol. lviii. p. 325; vol. lx. p. 55; Krehl 
and Matthes, ibid., vol. lx. p. 501. 



390 CLINICAL PATHOLOGY 

appear in the urine do not differ from those present in health. 31 
The urea is relatively reduced and the ammonium salts of 
organic acids increased. 32 The increase in the amount of these 
organic acids in the blood is the probable cause of the diminu- 
tion in the amount of carbon dioxide that is present there. 33 
As a rule, the creatinin is also increased in the urine. We have 
no positive information as to the amount of uric acid formed 
during fever. 

The excessive proteid decomposition in fever is caused in 
part by the elevation of temperature. 34 If a fasting animal be 
heated, the proteid decomposition is always increased, though 
if it is taking large amounts of food, this increase is little or 
not at all greater than would be the increase in the nitrogenous 
metabolism of normal animals under the same conditions. 
So far as man is concerned, it has also been shown that if the 
temperature is artificially raised as high as 39 C, the proteid 
decomposition is not greatly affected ; whereas, if the tempera- 
ture reaches 40 C. or over, an increase in proteid decomposi- 
tion always takes place. 35 

On the other hand, it is certain that the increased proteid 
destruction during fever is caused only in part by the elevation 
of temperature, for in fever this destruction is considerably 
greater than it is in artificial overheating of the body. This 
extra proteid decomposition may be due in part to the inani- 
tion, but it is especially due to the direct action of the toxic 
agent that causes the fever. In this respect it resembles the 
excessive nitrogenous metabolism present in certain cases of 
carcinoma, etc. 

31 Bohland, Pfliiger's Arch., vol. xliii. p. 30 ; Gumlich, Ztft. f. phys. 
Cherri:, vol. xvii. p. 10. 

32 Bohland, loc. cit. 

33 See G. Klemperer, Kongr. f. in. Med., 1890, p. 391. 

34 The observations to the contrary have been explained by F. Voit, 
Sit7.ungsber. d. Ges. f. Morph. u. Physiol, in Miinchen, 1895, Heft II. 

35 Linser and Schmid, Arch. f. klin. Med., vol. lxxix. p. 514. 



FEVER 391 

This hypothesis — that the excessive proteid decomposition 
in fever is largely due to toxic influences — is supported by the 
fact that no success has hitherto attended the attempts to cause 
the proteid metabolism in fever to follow the same lines as it 
does in health. These excessive decompositions may, indeed, be 
lessened by the administration of large quantities of carbo- 
hydrates and fats, 36 but not to the same extent as it is in the 
normal individual. 37 

The Non-Nitrogenous Metabolism during Fever. — It is 
uncertain to what extent the non-nitrogenous constituents of 
the proteid molecules are consumed in fever. The increased 
heat production might all be accounted for, if we assume that 
the affected proteids are completely burned. 3S If this were 
the case, then there should be no consumption of the fat or of 
the glycogen in the body. Yet we know, as a matter of fact, 
that glycogen is rapidly consumed in fever, and that patients 
with fever do not seem able to lay up any great store of this 
carbohydrate. 39 It would be interesting to determine quan- 
titatively the total heat production and the total glycogen of 
the body in fever, and so to discover if there is a retention 
in the body of some non-nitrogenous constituents of the pro- 
teid molecules, possibly as fat. 

The respiratory quotient in fever may not differ from the 
normal quotient, 40 yet in many infectious processes, as in 
erysipelas, typhoid fever, pneumonia, etc., it has frequently 
been found to be abnormally low. 41 This low respiratory 

88 Weber, Arch. f. exp. Path., vol. xlvii. p. 19. 

87 For the opposing view, see Hirschfeld, Berl. klin. Wochens., 1891, 
Nos. 2 and 8; May, Ztft. f. Biol., vol. xxx. p. 1. 

"Senator, Untersuchhungen utrer d. fieberhaften Prozess, Berlin, 1873; 
Kraus, Ztft. f. klin. Med., vol. xviii. p. 160; May, loc. cit. 

B0 Hirsch and Roily, Arch. f. klin. Med., vol. lxxv. p. 307; Roily, ibid., 
vol. lxxviii. p. 248; Ott, ibid., vol. lxxi. p. 263. 

40 F. Kraus, Ztft. f. klin. Med., vol. xviii. p. 160. 

41 Regnard, Resherches sur lcs combustions respiratoires ; Riethus, 
Arch. f. exp. Path., vol. xliv. p. 254. 



392 CLINICAL PATHOLOGY 

quotient depends not upon the temperature itself, but upon the 
cause of the fever, for it has been also found during the afebrile 
periods of an intermittent fever. There is no reason to believe 
that it depends upon an increased elimination of the carbon 
dioxide by other channels than the lungs, as by the skin or the 
urine. 42 This low respiratory quotient would therefore seem 
to indicate the retention in the body of some compound rich 
in carbon and oxygen. 

Diabetic patients frequently eliminate no sugar in their 
urine during fever; but we need further observations on this 
point in order to be certain that this is not an effect of the 
altered diet. In some cases the elimination of sugar has been 
found to be greater during fever than during health, and some 
believe that this is even the rule in diabetes. 43 It is well known 
that alimentary glycosuria may be induced with unusual ease 
in fever patients, thus showing that their tolerance for sugar 
is diminished. 44 Dogs from which the pancreases have been 
removed do not show any uniform variations in their carbo- 
hydrate metabolism during fever. 45 

So far as we know, no changes in fat metabolism occur 
during fever. It is apparently carried on precisely as in any 
other condition of under-nutrition. 

The Cause of the High Temperature in Fever. — We have 
already said that a rise in temperature must always be due to 
a disproportion between the heat production and the heat loss 
in the body. Since the production of heat in fever is greater 
than in health, it is theoretically possible that this increased 
production of heat may be the sole cause of the high tem- 
perature. Yet we know that much larger amounts of heat 

42 Scholtz, Arch. f. exp. Path., vol. xl. p. 326. 

43 Mohr, Ztft. f. klin. Med., vol. xlii. p. 402. 

44 De Campagnolle, Arch. f. klin. Med., vol. lx. p. 209; Strauss, Ztft. 
f. klin. Med., vol. xxxix. p. 202. 

46 Nebelthau, Arch. f. exp. Path., vol. xlvi. p. 385. 



FEVER 393 

may be produced in the normal individual by muscular ex- 
ertion and by a large proteid meal, and that these do not 
ordinarily cause any marked rise in temperature. It seems 
probable, therefore, that in fever the fault lies in the mechan- 
ism which regulates the heat loss, and we have already ex- 
pressed the view that, for some reason, the heat in fever is 
produced in such a manner that it does not furnish the normal 
stimulus to the mechanism that increases heat loss. Yet so 
long as we are ignorant as to the nature of the stimuli that 
normally increase the loss of heat from the body, it seems 
unprofitable to discuss the pathological changes which these 
stimuli may undergo. 

The Site of the Heat Production in Fever. — The character 
of the metabolic changes in fever give us no definite idea as 
to the tissues especially affected, for the appearance of such 
abnormal products as the albumoses and oxyacids in the urine 
signify nothing more than that the destruction of the cellular 
constituents of the body is increased. The evidence in favor 
of an increased consumption of red blood-corpuscles is very 
inconclusive. Neither the increased amounts of potassium salts 
in the urine nor the abnormal pigments there present can be 
considered to prove a wide-spread destruction of these ele- 
ments, and the blood picture itself is directly opposed to such 
an assumption. 

Observations on the temperature of the blood returning 
from various parts of the body do, however, give us some data 
as to the site of the heat production. Heidenhain and Kor- 
ner 4C found that when artificial fever had been produced in 
dogs by the injection of pus, the blood returning from the 
legs was warmer than that in the right ventricle. Numerous 
other observers have since shown that, in artificial fever, the 
venous blood returning from the kidneys, and especially from 

" Pfliigcr's Arch., vol, iii. p. 562. 



394 CLINICAL PATHOLOGY 

the liver, is warmer than that from the muscles and the skin. 47 
From these observations, we may infer that the excessive heat 
of fever is produced mainly in the large glands and the mus- 
cles, but to what extent each of these participates in its pro- 
duction is very uncertain. 

Since the glycogen of the body is consumed during fever, 
and since the same occurs when artificial fever is produced by 
puncture of the brain, 48 it would seem possible that the cause 
of the increased heat production in ordinary fever is a stimula- 
tion of the central nervous apparatus, which is similar to that 
induced by the puncture. Yet we must remember that it is 
possible to have septic fever without there being any glycogen 
in the liver, whereas the puncture of the brain produces no 
elevation of temperature under these circumstances. While we 
might assume, therefore, that the consumption of the glycogen 
in fever resulted from a stimulation of the nervous system, this 
hypothesis would not offer an explanation for the characteristic 
destruction of proteid material and for the fact that fever may 
occur in the absence of glycogen. 

The hypothesis that the increased heat production in fever 
is merely an acceleration of normal metabolism — that it is 
due, in fact, to an " increased chemical tone" — meets with the 
"serious objection that the metabolism in fever is not only quan- 
titatively increased, but is qualitatively altered, especially as 
regards the consumption of proteids. 

It seems to me very probable that the agent causing the 
fever actually destroys the cell proteids in various parts of 
the body. What becomes of the non-nitrogenous constituents 
of the injured proteid molecules is at present unknown to us. 

47 Krehl and Kratzsch, Arch. f. exp. Path., vol. xli. p. 185; Hirsch 
and Muller, Arch. f. klin. Med., vol. lxxv. p. 287 ; Zuntz, Ztrbl. f. d. med. 
Wiss., 1882, p. 32. 

48 Hirsch and Roily, Arch. f. klin. Med., vol. lxxv. p. 307; Roily, ibid., 
vol. lxxviii. p. 248. 



FEVER 395 

Yet exact information on this point appears to be essential 
before we can explain the abnormal course of the metabolism 
in fever and the fact that the heat formed does not furnish a 
sufficient stimulus to the mechanism that controls heat loss. 

The Heat-Regulatory Mechanism in Fever. — In the 
healthy individual a proper heat regulation cannot be main- 
tained unless certain parts of the mid-brain are intact. If these 
be destroyed, or if the spinal cord be cut at a high level, the 
temperature depends largely upon that of the surroundings, 
just as is the case in cold-blooded animals. 

It would seem probable that this nervous mechanism, which 
regulates the temperature of the body, is diseased in fever. 
The observations bearing on this question have dealt, for 
the most part, with the effect of procedures which withdraw 
heat from the body, and experiments on men as well as ani- 
mals have shown that if heat be artificially withdrawn from 
the body by cold baths, etc., then the compensatory increase 
in the heat production is less if the animal has a fever than 
if it be normal. In certain experiments on animals, indeed, 
there may be absolutely no increased production of heat under 
these circumstances. 49 

It follows that the temperature of febrile animals is more 
readily reduced by artificial cooling than is that of normal 
animals, and that, other things being equal, the patient with 
fever may be cooled off with comparative ease. It is also prob- 
able that his temperature may be more easily raised by arti- 
ficial means. For example, animals more readily acquire a 
high temperature from warm surroundings if they have been 
previously treated with injections of pus. 50 In apparent con- 

48 Licbermeister, Path. d. Ficbcrs, p. 341 ; Colasanti, Pfliiger's Arch., 
vol. xiv. p. 125; Finklcr, ibid., vol. lix. p. 98; Zuntz, Du Bois' Arch., 1882, 
P- 43- 

00 Dobrzanski and Naunyn, Arch. f. exp. Path., vol. i. p. 181; Finklcr, 
loc. cit. 



396 CLINICAL PATHOLOGY 

tradiction to these facts is the observation that the temperature 
of an animal with fever is sometimes made higher by exposure 
to cold, possibly because the cold increases the heat production 
within the body. Narcotic drugs render it impossible to pro- 
duce fever by certain artificial means, 51 probably because they 
effect the heat regulating centres. 52 

It is a matter of common clinical experience that the tem- 
perature of patients with fever is less resistant to external 
influences than is that of normal individuals. This lack of 
resistance differs in amount in different diseases and may even 
vary at different periods of the same disease. During typhoid 
fever, for example, the temperature can usually be reduced 
more readily in the later than in the earlier weeks of the illness. 
One reason why fever patients are particularly susceptible to 
the antipyretic action of the cold bath is, that their cutaneous 
vessels react abnormally to stimuli. It is when these vessels 
remain dilated for a considerable period after the cold bath 
that the most marked falls in temperature occur. 53 The anti- 
pyretic drugs also reduce the temperatures of fever patients 
much more effectually than they do those of normal indi- 
viduals; and here again these drugs are not equally effective 
in all cases nor in the same case at all stages of the disease. 54 
Thus we see that the temperature does not resist external influ- 
ences during fever so well as it does during health, and that 
this is so, partly because the regulatory mechanism is less ef- 
fective, and partly because the peripheral blood-vessels react 
abnormally to stimuli. 

Even during the convalescence from infectious diseases, 
the temperature regulation is often imperfect. Patients, who 
are recovering from typhoid fever, for example, easily acquire 

61 Mendelson, Virch. Arch., vol. c. p. 274. 

62 Rumpf, Pfliiger's Arch., vol. xxxiii. p. 538. 

63 Finkler, Kongr. f. in. Med., 1888, p. 314. 

54 Gottlieb, Arch. f. exp. Path., vol. xxvi. p. 419; vol. xxviii. p. 167. 



FEVER 397 

an elevation of temperature after eating large amounts of food 
or after excessive exercise; apparently because they cannot 
eliminate the large quantity of heat that has been suddenly 
liberated in their bodies. An analogous condition is seen in 
many captive animals, and it seems as if their temperature 
regulation is injured to a certain extent by the life of cap- 
tivity. Thus Finkler has observed a temperature of 40 C. 
(104 F.) in starving guinea-pigs after a full meal. 

All these facts point to some changes in that part of the 
brain which regulates the body temperature. The question 
naturally arises, Will patients with fever eliminate normally 
the extra heat that is set free in the body when large quanti- 
ties of proteid food are taken, or when the individual exercises ? 
Unfortunately, we have but little satisfactory evidence on 
these points, for, in the first place, it is not easy to feed fever 
patients with large amounts of food, 55 and in the second, the 
observations that muscular exercise tends to elevate the tem- 
perature of tuberculosis patients 56 do not, to my mind, settle 
this question decisively. Nevertheless, some importance must 
be allowed to the clinical observations that large amounts of 
food and much exercise tend to elevate the temperature of 
weakly individuals, convalescents, and of those with slight 
fever; and it really seems as if these patients eliminate the 
extra heat produced less well than do normal individuals. Lang 
has found that after taking food there is an increased elimina- 
tion of water from the bodies of both normal and feverish 
individuals, though it is slightly less in the latter. 57 Since 
he has also shown that the fever itself does not affect the elimi- 
nation of water from the skin, it would appear as if the fever- 
ish patient is able to eliminate the extra heat that follows the 

05 For this reason the results of Bauer, Arch. f. klin. Med., vol. xxiv. 
p. 60, and of v. Hosslin, Virch. Arch., vol. lxxxix. p. 95, are not decisive. 
M Ito, Diss. Erlangen, 1899. 
"Lang, Arch. f. klin. Med., vol. lxxx. p. 353. 



398 CLINICAL PATHOLOGY 

taking of food fairly well, even though he does not eliminate 
the extra heat which causes the fever. 

The elevated temperature of fever is produced mainly 
by the insufficient loss of heat from the body. Possibly, in- 
deed, this is the primary factor that causes the rise in tem- 
perature, though it seems more probable to me that the exces- 
sive heat production is also of some importance. Various 
possibilities as to the causal relation between these two pro- 
cesses must be considered. In the first place, the cause of the 
fever may affect primarily the central nervous system, pro- 
ducing, on the one hand, an increased production of heat, 
and, on the other, an insufficient elimination. Liebermeister, 58 
advanced such an hypothesis, — viz., that in fever the heat regu- 
latory centre is " set at a higher level" than normal, and that 
it tends to maintain the temperature of the body at this new 
level in the same way that it usually tends to maintain the 
normal temperature. We now know, however, that the tem- 
perature in fever is not maintained at its new level with the 
same degree of resistance to external influences as it is in 
health. 

According to a second hypothesis, the essential feature of 
fever is the insufficient heat elimination, the increased pro- 
teid destruction being non-essential and of the same character 
as that seen in various cachectic diseases. 

To my mind, however, it seems most probable that the 
agent causing the fever destroys the proteids and glycogen 
of the body in some abnormal manner, and so increases the 
heat production. The products of this abnormal metabolism, 
however, do not cause a sufficient elimination of heat, either 
because they do not furnish the proper stimulus to the heat 
regulating mechanism, or because the irritability of this mech- 
anism has been reduced in some peculiar manner. 

68 Path. d. Fiebers. 



FEVER 399 

The Causes of Fever, (a) Bacteria. — Various causes may 
give rise to fever. In the first place, fever may be produced by 
the entrance of living or dead bacteria, or of their products, 
into the blood. Yet the mere presence of micro-organisms in 
the circulation does not necessarily raise the temperature of 
the body, and many bacteria which produce fever in certain 
animals will fail to do so in others. Indeed, an animal may 
die from an infection and its heat production may be markedly 
increased, and yet, on account of the elimination of the extra 
heat from the body, there may be no rise of temperature. 59 
Protozoa may also give rise to fever, as in the case of malaria 
and of certain experimental infections. 60 

The substances that cause the fever are very possibly of a 
proteid nature, for complex substances isolated from the bodies 
of bacteria may give rise to fever if injected into men or 
animals. 61 It is questionable, however, whether these sub- 
stances are themselves proteids, or whether it is merely diffi- 
cult to separate them from proteids. Some have attempted 
to show that there is a non-proteid, fever-producing substance 
common to all bacteria, 62 but the evidence of this is very incon- 
clusive. 

(b) Aseptic Fevers. — Though bacteria and bacterial prod- 
ucts are undoubtedly the most important causes of fever, they 
are not the only ones. Fever may be produced by the destruc- 
tion of large numbers of cells in the body, even though micro- 
organisms play no part in the destructive processes. As 
examples of such, we may recall the fever that so frequently 



M Ricthus, Arch. f. exp. Path., vol. xliv. p. 253. 

eo Pfciffer, in Penzoldt-Stintzing's Handbuch; Krehl and Matthes, 
Arch. f. exp. Path., vol. xxxviii. p. 284. 

"II. Buchner, Berl. klin. Wochens., 1890, No. 10, and Munch, med. 
Wochens., 1891, No. 49; Krehl, Arch. f. exp. Path., vol. xxxv. p. 222. 

" Centanni, Deut. med. Wochens., 1894, Nos. 7 and 8; Voges, Ztft. f. 
Hyg., vol. xvii. p. 474. 



400 CLINICAL PATHOLOGY 

follows a simple fracture, 63 or that which may follow large 
interstitial hemorrhages. The fibrin ferment which is formed 
during the coagulation of blood may also cause an elevation 
of temperature. 64 

The fact that fever may be produced by bodies not derived 
from bacteria has led to careful studies concerning the action 
of numerous chemical substances upon the temperature of 
warm-blooded animals. 65 These studies have demonstrated 
that fever may be produced by the injection of various forms 
of proteids, whether the latter are assimilated or not, and 
whether they be of complex or comparatively simple structure. 
Elevations of temperature also follow the injection of many 
organic compounds and salts. Different animals, however, 
differ in their susceptibility to the action of these substances. 

Is it not possible that a single chemical substance or class 
of substances is the cause of all fevers? Some have thought, 
for example, that the fibrin ferment might play such a role, but 
Hammerschlag 66 has shown that in many fevers this substance 
is not increased in the blood. 

Albumoses, on the other hand, may be demonstrated in 
the urine of nearly all fever patients, whether the fever was of 
infectious or of other origin. 67 It is thus certain that proteid 
material undergoes hydrolytic cleavage during all forms of 
fever, even those caused by the introduction of simple chemi- 
cals into the body. The introduction of albumoses themselves 
into the body will give rise to fever, though it is possible that 
some contamination in the albumoses is the immediate cause 

83 Volkmann and Genzmer, Volkmann's klin. Vortr., No. 21. 

84 Edelberg, Arch. f. exp. Path., vol. xii. p. 283. 

65 Krehl, Arch. f. exp. Path., vol. xxxv. p. 222 ; Krehl and Matthes, 
Arch. f. klin. Med., vol. liv. p. 39; Klemperer, Naturforcherversammlung, 
1903, vol. ii. p. 67. 

68 Arch. f. exp. Path., vol. xxvii. p. 414. 

67 Krehl and Matthes, Arch. f. klin. Med., vol. liv. p. 501; Schultess, 
Arch. f. klin. Med., vol. lviii. p. 325 ; vol. lx. p. 55. 



FEVER 401 

of the elevation of temperature. 68 On the other hand, albu- 
moses may appear in the urine without there being any fever, 00 
so that if we assume that albumoses do cause fever normally, it 
is necessary to assume also that this effect can only result from 
certain forms of these proteids, and that other forms, not dis- 
tinguishable chemically, produce no such effect. 

At any rate, the proteid decomposition in fever pursues a 
peculiar course, and the hypothesis that the products of this 
abnormal decomposition directly cause the fever is an exceed- 
ingly attractive one. According to such an hypothesis, the sub- 
stances that produce the fever do so by primarily causing this 
abnormal proteid decomposition. The resulting products then 
give rise to the fever in the manner that has been already indi- 
cated. 

(c) Nervous Fevers. — It is probable, therefore, that the 
majority of all natural fevers are due to intoxications or in- 
fections. Some fevers are possibly of a different character, 
however, for it seems probable that the nervous centre which 
regulates the temperature of the body may be primarily dis- 
eased, and that it may be influenced by impulses from other 
parts of the central nervous system. Many observations, pur- 
porting to be examples of such a nervous fever, will not stand 
the scrutiny of a rigid criticism. For example, in poliomyelitis, 
porencephalitis, and meningitis the elevation of temperature 
is probably due to the infection ; while in other conditions, such 
as large cerebral hemorrhages, it may possibly be caused by 
the absorption of the fibrin ferment or of the products resulting 
from the destruction of large numbers of cells. 

In other conditions, the nervous lesion seems to exert a 
more direct influence upon the bodily temperature. At times, 
general convulsions, associated with stupor, lead to excessive 
elevations of temperature, and at other times, when the con- 

"Krehl and Matthcs, Arch. f. cxp. Path., vol. xxxvi. p. 437. 
69 See Schultess, Arch. f. klin. Med., vol. lx. p. 55. 
26 



402 CLINICAL PATHOLOGY 

vulsions are produced by certain drugs, there may be an actual 
reduction of temperature. 70 In the latter instances the heat 
regulation is affected, and it seems as if the poisons leading to 
the convulsions likewise diminished the production of heat in 
the body. 

We know that muscular movements will raise the tempera- 
ture of even a healthy person, if the elimination of heat is in- 
terfered with, which fact has also been proved experimentally 
on animals. 71 If, however, the extra heat that is liberated 
during exercise can be eliminated, no rise of temperature re- 
sults. As a rule, therefore, convulsions do not materially alter 
the body temperature. A rise of temperature is especially apt 
to be produced by convulsions when there is reason to believe 
that the heat-regulating mechanism is paralyzed. 72 For exam- 
ple, fever is rarely present in the earlier stages of tetanus, and 
the rise of temperature toward the end of the disease would ap- 
pear to be caused by a paralysis of the heat-regulating centre. 
The high temperature that has been observed in many cases of 
status epilepticus is probably to be explained in a similar man- 
ner. Possibly, also, the elevations of temperature in hysterical 
individuals, which have been described by some writers, are 
of this character, 73 though, never having witnessed a true 
hysterical fever, I personally feel somewhat sceptical as to its 
existence. 

In another group of cases, fever is associated with gross 
lesions of the central nervous system, and neither infection, 
resorption of the products of tissue disintegration, nor con- 
vulsions can be held responsible for its presence. Brain tumors 

70 See Harnack and Schwegmann, Arch. f. exp. Path., vol. xl. p. 151 ; 
Harnack, ibid., vol. xlv. pp. 45, 447. 

"Leyden, Virch. Arch., vol. xxvi. p. 538; Kionka, Internat. Arch. f. 
Phar., vol. v. p. III. 

72 Wunderlich, Arch. f. Heilkunde, 1864, p. 205; Erb, Arch. f. klin. 
Med., vol. i. p. 175. 

73 Dippe, Arch. f. klin. Med., vol. lxiv. p. 212. 



FEVER 403 

and other pathological conditions may thus produce a fever, 
and it seems very probable that the elevation of temperature 
is then due to the direct action of these pathological processes 
upon the mechanism regulating the heat of the body. 

Experimentally, it is possible to produce fever in animals 
by injuring the brain. Injuries to various parts of the cere- 
brum will sometimes cause an elevation of temperature, but this 
elevation can be caused in almost every case if a long needle 
be thrust into the mid-brain of rabbits. 74 The fever pro- 
duced by such a puncture begins several hours after the opera- 
tion and continues for days. It may reach a considerable 
height. The production of heat in the body is increased, and 
the loss of heat is also increased, but to a lesser degree. The 
loss of heat by evaporation from the skin is relatively greater 
than it is in the case of infectious fevers. Furthermore, the 
increased heat production is almost entirely due to the increased 
consumption of non-nitrogenous material, which fact also 
serves to differentiate this from ordinary fever, in which a 
characteristic hydrolytic cleavage of proteids takes place. 75 
During the fever resulting from a puncture of the brain the 
liver is the warmest organ of the body, 70 and the glycogen 
stored up there rapidly disappears. Indeed, unless there is a 
store of glycogen in the body, no rise in temperature follows 
the puncture of the brain. 77 It is therefore apparent that the 
elevation of temperature caused by puncture of the brain 
differs from that due to an infection in several important 
particulars. 

It is very questionable whether fever is ever caused by 

7< Aronsohn and Sachs, Pfliiger's Arch., vol. xxxvii. p. 232 ; Gottlieb, 
Arch. f. exp. Path., vol. xx. p. 167; Schultzc, Arch. f. exp. Path., vol. 
xliii. p. 193; Aronsohn, Virch. Arch., vol. clxix. p. 501. 

"Roily, Arch. f. klin. Med., vol. lxxviii. p. 289; Martin, Arch. f. exp. 
Path., vol. xl. p. 453. 

"Hirsch and Roily, Arch. f. klin. Med., vol. lxxv. p. 307. 

" Roily, loc. cit. 






404 CLINICAL PATHOLOGY 

reflexes. The elevations of temperature which may occur dur- 
ing biliary colic and those which may follow urethral opera- 
tions (catheter fever) are often regarded as instances of reflex 
fevers. Yet, in my opinion, it is much more probable that we 
are here dealing with fevers caused either by the absorption of 
toxic products or by actual infections. Possibly an investiga- 
tion into the metabolism in such cases might give some indica- 
tion as to the true nature of the fever. 

Elevations of temperature have been observed after in- 
juries to the spinal cord. Such elevations occur most fre- 
quently in association with severe contusions of the cervical 
region, produced by fractures of the corresponding vertebrae. 
Temperatures as high as 42 ° to 44 ° C. (106.5 to in F.) 
have been observed in such conditions. 78 It is possible to pro- 
duce the same effect experimentally by crushing the upper- 
most part of the cervical cord of large dogs. 79 After such in- 
juries the temperature does not always become elevated, and it 
may, indeed, fall. These varying results of the experiment 
are due to the fact that, if the cord of a warm-blooded animal 
be severed high up, the body temperature becomes a play- 
thing of circumstances. When the temperature of its sur- 
roundings is high, the heat production is increased, and when 
the surrounding temperature is low, the heat production is 
diminished ; in other words, there is no regulation of the pro- 
duction of heat in the body. 80 This is one reason why animals 
easily become overheated or cooled off after they have sus- 
tained severe contusions of the cervical cord. 

Other factors besides the surrounding temperature also 
play a part in the elevation of the temperature that takes place 
in cord injuries, though upon these points we are less certain. It 
is possible, for example, that the peripheral circulation is so 

78 v. Recklinghausen, Allg. Path., p. 463. 

'* Naunyn and Quincke, Arch. f. Anat. u. physiol., 1869, pp. 174, 521. 

80 Pfliiger, Pfliiger's Arch., vol. xii. p. 282. 



FEVER 405 

altered that the loss of heat from the body is diminished. Fur- 
thermore, the crushing of the cord, which manner of injury 
seems to be an important requisite for a high temperature, may 
possibly produce an irritation of the corresponding muscles, 
and so directly increase the production of heat in the body. 
This is apparently the reason why the elevation of temperature 
is more likely to take place in men and large dogs than it is 
in small animals. The former have a relatively small surface 
from which to lose heat and a relatively large musculature in 
which an increased heat production can take place. We see 
therefore that the rise of temperature that may follow cord 
injuries is due, partly, to a loss of heat regulation, and partly, 
in all probability, to an increased production and a diminished 
loss of heat from the body. The condition, therefore, differs 
essentially from that present in true fever. 

The Causes of Variations in the Clinical Picture of Fever. 
— These depend, in the first place, upon the cause of the fever. 
Most fevers are of bacterial origin, and, as is well known, bac- 
teria may vary in their virulence, conditions of growth, and 
duration of life. So far as malarial fever is concerned, we 
know that the paroxysms occur when the causative organisms 
are at a particular stage of development. 

In the second place, the clinical picture presented by fever 
depends largely upon the condition of the individual affected ; 
upon his strength, nutrition, and degree of immunity. During 
epidemics, different symptoms occur in different individuals. 
We may say, in general, that young and strong patients react 
with a higher fever to an infection than do old and weakly 
ones. Indeed, the temperature may actually fall in the latter 
class of patients. We possess analogous experimental observa- 
tions, for it is impossible to produce fever by the injection of 
certain chemicals into fasting animals, whereas the same 
chemicals will regularly cause a fever in well-fed animals. 81 
a Krchl and Matthes, Arch. f. cxp. Path., vol. xl. p. 430. 



406 CLINICAL PATHOLOGY 

Bacterial infections, on the other hand, may cause an elevation 
of temperature whether the animal be starving or well fed. 

The numerous other symptoms seen in fever are also sub- 
ject to considerable variations. These depend in part upon the 
height of the temperature, for this influences the rate of the 
proteid and other decompositions, as well as the cardiac and 
respiratory rates. Yet no exact ratio exists between the se- 
verity of these symptoms and the degree of temperature, be- 
cause other factors, especially toxic influences, play so great a 
role. This has already been discussed so far as the pulse-rate 
is concerned (see page 79). 

Indeed, we may say, in general, that the symptoms of 
intoxication predominate in the clinical picture of fever, and 
that many of the phenomena which were formally attributed 
to the high temperatures are now ascribed to the action of 
toxins. Thus the psychic changes, the gastrointestinal dis- 
turbances, and the susceptibility of the respiratory tract to 
complicating inflammations, all these are of toxic rather than of 
thermic origin. They are rarely seen in the " aseptic fever" fol- 
lowing simple fractures, and they are most prominent in such 
pronounced intoxications as typhoid fever. These symptoms 
also depend to a certain extent upon individual peculiarities, 
and heavy drinkers, for example, are very prone to show 
serious nervous manifestations. 

The Nutrition in Fever. — The nutrition is always impaired 
in fevers of long duration, partly because of the increased pro- 
teid consumption, partly because the patients do not take a 
sufficient quantity of food. Their appetites are often very 
poor, though this may not be the case in the hectic fever of 
tuberculosis. For these reasons most patients with fever be- 
come emaciated and weak, and the weakness is often greater 
than can be accounted for by the lack of food alone; being 
dependent, as we have seen, upon the excessive consumption 
of the proteid material of the body. 



FEVER 407 

On the other hand, in long-continued infections, a tend- 
ency to limit the metabolic processes is often manifest, and in 
the terminal stages of chronic diseases the proteid decomposi- 
tion and the total oxidations in the body often reach a sur- 
prisingly low level. This adaptation enables many a person to 
undergo a long-continued illness which would otherwise prove 
fatal. Though the excessive consumption of proteid material 
is common to all forms of fever, it seems very probable that 
certain infections are particularly harmful in this respect. 

The cause of the various forms of cellular degeneration that 
occur so frequently in fever is not yet definitely determined. 
Some believe that the high temperature may cause the degen- 
erative changes, 82 whereas others hold that the temperature 
alone will not produce them. 83 It is impossible at present to 
reconcile these varying views. 

The Water Retention in Fever. — Years ago, Ley den 84 
•made the observation that patients with fever frequently lose 
but little weight during the course of the acute process, — i.e., 
at the time when the consumption of material in the body is 
most active, but that the principal loss in their weight takes 
place during convalescence. He explained these results by as- 
suming that there is a retention of water in the body during 
fever. From that time up to the present this question has 
awakened general interest. 

Yet we need more accurate data concerning this retention 
of water in fever, for not all investigated cases have yielded 
identical results. 85 Indeed, a complete and accurate determina- 
tion of the water losses in fever has never been made. As a 
rule, the urine is diminished in quantity, and the absolute loss 

82 Licbcrmeistcr, Path. d. Ficbers, p. 427; Litten, Virch. Arch., vol. 
lxx. p. 10; Zicglcr, Kongr. f. in. Med., 1895, p. 345; Werhowsky, Zieg- 
ler's Beitr., vol. xviii. p. 72. 

83 Naunyn, Arch. f. exp. Path., vol. xviii. p. 49. 

M Arch. f. klin. Med., vol. v. p. 366. 

"See Kohlschiitter, Volkmann's Beitr., No. 303. 



408 CLINICAL PATHOLOGY 

through the skin is equal to or less than that in health; but 
the loss through the lungs is increased. 86 From these isolated 
observations it is impossible to tell accurately whether the total 
loss of water from the body is increased or diminished during 
fever. The low quantity of chlorides in the urine during cer- 
tain fevers has been explained on the assumption that a salty 
liquid is retained in the body ; but, in our opinion, this assump- 
tion is hardly justified. 

Despite our lack of direct observations on these points, it 
seems highly probable that a retention of water does take place 
in the bodies of many fever patients. The exact conditions 
upon which this retention depends are, however, at present 
unknown to us, though we know that various cachectic condi- 
tions, such as carcinomatosis, may lead to a retention of water 
in the body. In another place we have expressed the view that 
an insufficient evaporation from the skin was one of the main 
causes of the heightened temperature of fever. 

The Significance of Fever. — Whether or not the elevation 
of temperature is of advantage to the infected organism is a 
subject that has engaged the attention of physicians from the 
most remote times down to the present. Three conflicting- 
views have been advocated. According to the first, the eleva- 
tion of temperature is in itself dangerous to the patient, 87 and 
may even be the cause of death; according to the second, the 
danger of the infectious process depends only to a very slight 
extent upon the high temperature ; and according to the third, 
the high temperature is advantageous, for by this means the 
infected body is " cleansed by fire." 8S The treatment of fever 
must depend to a large extent upon the view that is accepted, 
consciously or unconsciously, by the physician. 

80 Lang, Arch. f. klin. Med., vol. lxxix. p. 343. 
87 Liebermeister, Path. d. Fiebers, p. 423. 

s8 Pfluger, Pfluger's Arch., vol. xiv. p. 502 ; see Unterricht, Volkmann's 
Vortr., N. R, No. 159. 



FEVER 409 

Is the elevation of temperature in the course of an infec- 
tion useful, harmful, or of no particular significance ? So long 
as the elevation remains within moderate limits, it may cer- 
tainly be regarded as relatively harmless. The rapid pulse 
and respirations, the loss of appetite, and the possible paren- 
chymatous degenerations of the organs, in so far as they are 
directly caused by the temperature, are not in themselves very 
dangerous. If, on the other hand, the elevation of temperature 
is very great, it may certainly be harmful and the same dangers 
are threatened as in a heat stroke. Yet such dangerously high 
temperatures are comparatively rare in fever, and the reason 
why a high temperature is generally regarded as a bad sign in 
an infectious disease is that it indicates a severe infection. This 
is well illustrated by the fact that high temperatures in malaria 
are generally regarded with a certain amount of indifference, 
whereas the same temperatures in typhoid fever or pneumonia 
would be looked upon with alarm. 

Whether the elevation of temperature is directly bene- 
ficial to the infected organism or not, is a question that is 
not so easily settled. In recent years there has been a tendency 
to apply the Darwinian theory to pathological processes in 
general, and to say, for example, that fever could never have 
survived throughout immeasurable time were it not inherited 
as a useful weapon in the struggle for existence. Yet one may 
question to what extent the Darwinian theory applies to path- 
ological conditions, 89 and it seems equally reasonable to regard 
fever as a blind reaction against an injury, possibly useful or 
possibly harmful. The question is not one that can be solved 
by such philosophical considerations, and the final answer 
must be based upon established facts, derived either from bed- 
side observations or from animal experiments. 

Unfortunately, clinical studies have done little to solve this 
problem. We have, it is true, accumulated extensive statistics 
" See Ziegler, Munch, med. Wochens., 1896, No. 43. 



410 CLINICAL PATHOLOGY 

on the course of infectious diseases, especially of typhoid 
fever, under the expectant and the antipyretic forms of treat- 
ment. Yet, even though we acknowledge the advantage of the 
latter treatment, we are helped but little to a solution of our 
problem, for cold water not only lowers the temperature of the 
body, but it influences the disease in many other ways, and 
antipyretic drugs introduce abnormal chemical processes into 
the metabolism. 

It is possible that at a higher temperature the growth or 
virulence of the micro-organisms which cause the disease may 
be diminished. At present, however, we are unable to say 
definitely to what extent this actually occurs in disease. 

We do possess, however, a number of observations on the 
effect of increasing an animal's temperature after it has been 
artificially infected. Infections with diphtheria bacilli, chicken 
cholera bacilli, and pneumobacilli run a milder course in rab- 
bits if the temperature be artificially elevated by puncture of 
the brain, 90 and intoxications with hydrolytic ferments like- 
wise are less virulent at higher temperatures. 91 The same has 
been found to be true for erysipelas infections in rabbits, 92 and 
the number of such examples could be still further multiplied. 

Perhaps the action or formation of antibodies is favored by 
the high temperature. At any rate, Kast found that Pfeiffer's 
antibody against typhoid bacilli worked better at high tem- 
peratures, 93 though, on the other hand, antipyretic treatment 
does not seem to influence the formation of the immune body 
in man. 94 

We possess, therefore, some noteworthy experiments 
which support the view that the elevation of temperature dur- 

90 Loewy and Richter, Virch. Arch., vol. cxlv. p. 49. 

91 Hilderbrandt, Virch. Arch., vol. cxxi. p. I. 

92 Filehne, Jour, of Physiol., vol. xvii. 

93 Kast, Kongr. f. in. Med., 1896, p. 37 ; Paech, Diss. Breslau, 1900. 

94 Lemaire, Arch, internat. de pharacodyn., vol. v. p. 225 ; Schiitze, Ztft. 
f. Hyg., vol. xxxviii. p. 205. 



FEVER 411 

ing an infection is directly beneficial to the infected organism. 
It must be admitted, however, that only a beginning has been 
•made, and that more observations are necessary before the 
question can be regarded as definitely settled, and before we 
shall know whether it is the increased temperature itself or 
some associated changes in metabolism that benefits the patient. 

The Temperature in Collapse. — We have had frequent 
occasion to mention that the temperature during fever is sub- 
ject to great variations, and that it tends to rise or fall from 
relatively insignificant causes. A great fall of temperature 
during an infection has long been recognized as a dangerous 
symptom, mainly because it so frequently heralds the onset of 
collapse. Such a fall is especially apt to occur in weak indi- 
viduals. This has been observed experimentally. The ordinary 
fever-producing agents may cause a reduction in an animal's 
temperature if they are given in large amounts, or if the animals 
used are very " weak" or " non-resistant." It is difficult to say 
what constitutes this " weakness" or " lack of resistance" on 
the part of infected individuals, though it is very possible that 
the condition of the circulation plays an important role. 

Not only the resistance of the individual, but the kind and 
quantity of toxins are of importance in the production of col- 
lapse. The same substance that will give rise to fever in 
small doses will lead to collapse if given in large doses. This 
is well illustrated in the case of Koch's tuberculin. 93 If this 
substance be given to animals in very large doses, the produc- 
tion of heat in the body is actually diminished, and in the fatal 
cases only fifty-three per cent, of the normal amount of heat 
may be produced. At autopsy the vessels in the abdomen, and 
especially those belonging to the intestines, are found to be 
dilated. This finding agrees with the observations of Rom- 
berg, Passler, and Bruhns (see page 113), who showed that 

"Matthcs, Arch. f. exp. Path., vol. xxxvi. p. 437; vol. xxxviii. p. 299; 
Krehl, ibid., vol. xxxv. p. 222. 



412 CLINICAL PATHOLOGY 

the circulatory failure in infectious diseases is principally 
caused by a central vascular paralysis, affecting especially the 
splanchnic vessels. The dilatation of these vessels allows so 
much blood to collect in them that the heart is no longer prop- 
erly filled from the veins, the general blood-pressure falls, and 
the activity of the muscles becomes so reduced that, in spite of 
the fact that the heat losses are greatly diminished, the body is 
no longer able to maintain its normal temperature. Thus we 
see that the fall of temperature in collapse occurs at a time 
when less heat than normal is produced in the body. 

A certain antagonism exists, therefore, between fever and 
collapse. In fever, both the heat production and the heat losses 
are increased, the former being especially accelerated. In col- 
lapse, both of these are diminished, but the heat production 
is more diminshed than is the heat loss. On the other hand, 
fever and collapse resemble each other in certain respects, for 
in both too small an amount of blood passes through the cu- 
taneous vessels. 96 Indeed, they tend to shade into each other, 
and, as we have seen, the one or the other may result from the 
same cause, depending upon the factors already described. 

Subnormal Temperature. — Subnormal temperatures are 
seen not only during collapse from infectious diseases, but also 
after extensive injuries, severe hemorrhages, long-continued 
narcosis, perforative peritonitis, and various other severe 
lesions within the peritoneal cavity. It is possible that in 
many of these the same conditions are present as in collapse; 
yet it is quite wrong to regard all subnormal temperatures as 
symptoms of collapse. 97 

Subnormal temperatures are more common than is gener- 
ally supposed. They are often seen during convalescence from 
infectious diseases, and in such instances they are generally 
due to a diminished production of heat combined with an in- 

98 Maragliano, Ztft. f. klin. Med., vol. xiv. p. 309 ; vol. xvii. p. 291. 
07 Jannsen, Arch. f. klin. Med., vol. liii. p. 247. 



FEVER 413 

efficient heat regulation. A subnormal temperature frequently 
accompanies intoxication with alcohol or related drugs. These 
lessen the rate of oxidation in the body, — i.e., they diminish 
heat production and, in addition, they interfere with the mech- 
anism regulating the loss of heat from the skin. 9S Conse- 
quently, an intoxicated man is less able to withstand cold than 
is a healthy individual, and if exposed to cold, the temperature 
of his body is more liable to fall. 

When the temperature of the body becomes very low, nar- 
cosis and finally a general paralysis results. The narcosis will, 
in turn, favor a further lowering of the temperature, for the 
body can no longer increase its production of heat by muscu- 
lar activity. Even in ordinary sleep the heat regulation is less 
efficient than during the waking hours, and this lack of regula- 
tion is much more marked during deep narcosis. For these 
reasons, the danger of freezing to death is best combated by 
continued muscular movements, for these not only increase the 
production of heat, but they reduce the tendency to go to sleep. 

We do not know how low the temperature may fall without 
causing death, though it is certain that both men and animals 
have recovered from very low temperatures." 

"Rumpf, Pfliiger's Arch., vol. xxxiii. p. 538. 

09 Jannsen, loc. cit, and Cohnheim, All. Path., vol. ii. p. 489. 



CHAPTER XL 

THE SECRETION OF URINE. 

The major portion of the solid waste products that arise 
in the body leave it by way of the kidneys. We have already 
had occasion to describe many of these substances, and it is 
not our purpose to review in this place the origin of each one 
of them, but rather to deal with the mechanism of secretion 
itself; though it must be admitted that it is often impossible 
to draw a sharp line between this secreting mechanism and the 
products that are eliminated. 

The composition of the urine depends partly upon the con- 
dition of the secreting cells in the kidneys and partly upon the 
quality and quantity of blood which passes through these or- 
gans. These factors are more or less interdependent upon one 
another. For example, if the blood-stream through the kidneys 
be slowed, not only does less blood come in contact with the 
secreting cells but these cells are liable to suffer in structure 
and function. On the other hand, if the renal cells are prima- 
rily injured, this frequently affects the circulation through the 
kidneys. It is often very difficult, therefore, to tell which part 
of the renal apparatus is primarily affected. 

The Effect of an Increased Flow of Blood through the 
Kidneys. 1 — It is a general rule that the quantity of urine se- 
creted varies directly with the quantity of blood that flows 
through the kidneys. It likewise varies with the difference be- 
tween the pressure of the blood in capillaries and the pressure 
of the urine within the uriniferous tubules. (Finally it varies 
directly with the pulse pressure (the difference between the 
maximum and minimum blood pressures). 2 — Ed.) 

1 See Munk and Senator, Virch Arch., vol. cxiv. p. i ; Spiro and Vogt, 
in Asher-Spiro Ergebnisse, vol. i. p. 414. 

2 Erlanger and Hooker, Am. Jour, of Physiol., vol. x. 

414 



THE SECRETION OF URINE 415 

When the total quantity of urine is increased, the percent- 
age of solid materials present decreases, and vice versa; yet this 
percentage of solids nearly always remains within certain lim- 
its, rarely going above twelve per cent, or below three-tenths 
per cent. The relation between the total quantity of solids ex- 
creted and the total quantity of urine seems to be subject to 
considerable variation, and the different solids often vary 
independently of one another. The total quantity of urea, for 
example, varies directly with the quantity of blood that flows 
through the kidneys, whereas the total quantity of sodium 
chloride is almost independent of this blood-flow. 

Whenever more blood flows through the kidneys, therefore, 
the amount of urine is increased. The cause of the increased 
blood-flow may lie either in a higher arterial pressure, unac- 
companied by a corresponding contraction of the renal vessels, 
or it may be due to a local dilatation of these vessels, while the 
general blood-pressure remains constant. 

Many forms of chronic nephritis are accompanied by a high 
blood-pressure (see page 50), and this always causes an 
increased secretion of urine, if a sufficient number of function- 
ing renal cells are present and if the increase in. the general 
blood-pressure is not accompanied by a constriction of the renal 
vessels of such a degree that it would prevent a more rapid 
blood-flow through the kidneys. As we have said, the in- 
creased elimination of water in such cases reduces the per- 
centage of solids in the urine. The absolute excretion of the 
different solids, however, in these forms of nephritis varies 
greatly, 3 being dependent, apparently, to a great extent upon 
the condition of the epithelial cells. 

The increased blood-pressure that follows the administra- 
tion of digitalis to patients with heart disease also frequently 
causes an increased elimination of urine, because the renal 

"Fleischer, Arch. f. klin. Med., vol. xxix. p. 129; v. Noorden, Path. d. 

Stoffwech'-ds, p. 364. 



416 CLINICAL PATHOLOGY 

circulation is improved. Whether or not other conditions as- 
sociated with high arterial pressure, such as certain forms of 
arteriosclerosis and of " idiopathic" heart hypertrophy, like- 
wise increase the urine, is still uncertain. 

Diabetes Insipidus. — The second condition leading to an 
increased flow of blood through the kidneys is a local dilata- 
tion of their vessels, the arterial pressure remaining constant; 
as can be experimentally proven by cutting the renal nerves. 

Such a dilatation of the renal vessels is a possible cause of 
diabetes insipidus, a disease which is characterized clinically 
by the excretion of large amounts of dilute, sugar-free urine, 
without there being any associated increase in the general ar- 
terial pressure. The excessive amount of urine frequently car- 
ries out with it demonstrable quantities of inosite, and at times 
the total quantity of urea is also increased. This latter in- 
crease is caused by the large amounts of food eaten, for many 
of these patients, for some unknown reason, have excessive 
appetites, just as have patients with diabetes mellitus. 

We really know very little concerning the etiology of dia- 
betes insipidus. It certainly occurs sometimes as a family dis- 
ease. 4 In some cases the blood is more dilute than normal, 
and this may be instrumental in causing the polyuria ; yet this 
finding is by no means a constant one. At other times anatom- 
ical lesions of the cerebellum, the pons, or the medulla have 
been found at autopsy, 5 findings which well accord with the 
experimental observation that injuries to corresponding parts 
of the brain in animals may lead to polyuria. 6 Yet there is 
some uncertainty as to the exact part of the brain that must 
be affected in order to produce this increased flow of urine. 

4 Weil, Virch. Arch., vol. xcv. p. 70. 

5 Ebstein, Arch. f. klin. Med., vol. xi. p. 344; Hoffmann, Lehrbuch 
d. Konstitutionskr., p. 342. 

6 Claude Bernard, Legons de Phys. ; Eckhard, Beitr. z. Anat. u. Phys., 
4, 5, and 6. 



THE SECRETION OF URINE 417 

The evidence at our disposal, therefore, seems to favor the 
hypothesis that diabetes insipidus is due to some abnormal 
vasomotor influences, which cause a local dilatation of the 
renal arteries. It must be acknowledged, however, that this 
hypothesis does not explain very satisfactorily all of the symp- 
toms of diabetes insipidus, nor does it explain the relationship 
which seems to exist between this disease and true diabetes 
mellitus. 

The Effect of a Diminished Flow of Blood through the 
Kidneys. — If the quantity of blood that flows through the kid- 
neys be diminished, a small amount of highly concentrated 
urine is secreted, and the total excretion of urea is diminished. 

The cause of such a diminished blood-flow may be either 
local or general. Locally a contraction of the renal vessels will 
diminish the renal circulation, and it may do so even though 
the general blood-pressure be increased from a contraction of 
many other arteries. This local constriction of the renal arte- 
ries is the cause of the diminished secretion of urine in as- 
phyxia, in strychnine poisoning, and in epileptic and eclamptic 
convulsions. 

In the second place, a diminished renal circulation may 
occur in the absence of any local constriction of the renal ves- 
sels, either because the general arterial pressure is reduced or 
because the pressure in the renal veins is raised. The reduction 
of the general arterial pressure may result from a wide-spread 
vasomotor paralysis or from a weakening of the left ventricle. 
The pressure in the renal veins may be raised, either by an 
occlusion of these veins or of the vena cava inferior, by an in- 
crease in the general venous pressure from a weakening of the 
right ventricle, or by a diminution in the aspirating action of 
the thorax. The most marked effect upon the renal circula- 
tion will naturally be produced when a lowering of the general 
arterial pressure is combined with a rise in the venous press- 
ure. This combination occurs when both ventricles of the 

27 



418 CLINICAL PATHOLOGY 

heart are weakened, and this is, indeed, the most frequent cause 
of an insufficient flow of blood through the kidneys. It is met 
with in many varieties of cardiac disease, whether these affect 
the endocardium, the myocardium, or the pericardium. 

In many of these circulatory disturbances, proteids from 
the blood pass through into the urine ; yet, since this is prob- 
ably due to changes in the epithelial cells, we shall defer its 
consideration to another place. 

The Effect of an Obstruction to the Escape of Urine. — The 
obstruction to the escape of urine may be situated within the 
kidney itself. The uriniferous tubules may be compressed by 
scar tissue, or their lumina may be occluded by casts or by pre- 
cipitates of haemoglobin, bilirubin, uric acid, calcium salts, etc. 
It is questionable, however, if any of the precipitates, with the 
exception of haemoglobin, really oppose much resistance to the 
escape of urine and it is quite possible that they lie in the 
tubules merely because the amount of water secreted is in- 
sufficient to carry them away. 

On the other hand, the obstruction to the exit of urine may 
be situated outside of the kidneys, in the lower urinary pas- 
sages, and it may then be caused by calculi, tumors, scar tis- 
sue, etc. The effect which such obstructions exert upon the 
total quantity of urine secreted depends, in the first place, upon 
whether they obstruct the outflow from one or from both kid- 
neys. If the former be the case, the affected kidney will elim- 
inate less urine than normal, but the urinary material retained 
in the blood, will stimulate the other kidney and cause it to do 
extra work and to hypertrophy. The urine, as a whole, will 
not be greatly altered. 

The effect of an obstruction upon the secretory activity 
of the affected kidney depends largely upon the degree of ob- 
struction. If this be so complete that the urine is retained 
under a pressure amounting to sixty millimetres of mercury or 
more, the affected kidney ceases to secrete. If the obstruction 



THE SECRETION OF URINE 419 

be less complete, so that the urinary pressure above the obstruc- 
tion be less than sixty millimetres of mercury, then the secre- 
tion continues, but the rapidity of secretion diminishes in pro- 
portion as the pressure of retained urine increases. 7 The 
details concerning the cessation of secretion are not very well 
understood. At first, the retained urine merely serves to dis- 
tend the urinary passages. As the pressure increases, however, 
a portion of the urine appears to be resorbed through the cells 
of urinary tubules, which then become cedematous. Finally, 
the overfilled tubules and the swollen cells press upon the veins 
and capillaries and thereby diminish their size, and the rapidity 
of the flow of blood through the kidneys is lessened. This, in 
turn, diminishes the secretion of urine. 

If the obstruction to the flow of urine from a kidney be 
complete and permanent, then the corresponding kidney atro- 
phies, and only a moderate grade of hydronephrosis develops. 
If, however, the obstruction be incomplete, or if it be more or 
less intermittent, then the structure and the function of the 
kidney are but little affected. Its pelvis, however, gradually 
dilates, and an enormous hydronephrosis may be produced. 

The Effect of Lesions of the Secreting Membrane. — We 
have already mentioned the susceptibility of the renal epithe- 
lium to changes in the quantity and quality of blood that passes 
through the kidneys. Several membranes separate the blood 
in the capillaries from the lumina of the uriniferous tubules, — 
viz., the capillary walls, the basement membranes, and the epi- 
thelial cells. The possibility exists, therefore, that lesions of 
any one of these might render the secretory apparatus abnor- 
mally permeable. Apparently, however, lesions of the capillary 
walls are of comparatively little importance, and it may be said 
in general that the secretion depends rather upon the paren- 
chyma cells than upon the endothelial lining of the capillaries. 
Indeed, wide-spread amyloid degeneration of the renal capil- 
7 Hermann, Wiener Sitzungsber., vol. xlvii. p. 317. 



420 CLINICAL PATHOLOGY 

laries has been observed without any changes in the urine being 
present. 8 

All lesions of the epithelial cells, degenerative as well as 
inflammatory, and especially those lesions which involve the 
glomeruli, tend to diminish the secretion of water. Yet, in 
many cases of nephritis this tendency is more than neutralized 
by an associated increase in the amount of blood that flows 
through the kidneys, for, as we have seen, this tends to increase 
the excretion of urine. The quantity of urine, therefore, that 
is eliminated in pathological renal conditions depends mainly 
upon these two sets of factors : first, the degree and the extent 
of the damage to the secreting cells ; and secondly, the quantity 
and quality of blood which comes in contact with them. In 
wide-spread acute nephritis, the excretion of water is nearly 
always diminished, whereas in chronic diseases of the kidney, 
especially if these be of limited extent, the effects of the in- 
creased work of the heart, the high blood-pressure, and the 
good renal circulation predominates, and such patients fre- 
quently secrete even more urine than does a normal individual. 
When, however, cardiac failure appears, and the general blood- 
pressure falls, then the amount of urine secreted by these 
patients is immediately diminished. 

The excretion of solids follows about the same course as 
does that of the water, but less is known about them. Nitro- 
genous substances tend to increase with an increase in the 
quantity of urine ; yet no very strict parallelism exists between 
the two. Other substances, especially the chlorides, seem to be 
excreted in quantities that are, to a great measure, independent 
of the total quantity of urine. 9 

Albuminuria. 10 — Although it has been generally consid- 

8 Litten, Berl. klin. Wochens., 1878, Nos. 22 and 23. 

'Fleischer, Arch. f. klin. Med., vol. xxix. p. 129; v. Noorden, Deut. 
med. Wochens., 1892, No. 35, and in his Path. d. Stoffwechsels, p. 364. 

10 See Senator, in the Nothnagel System; Liithje, Ther. d. Gegenwart, 
November, 1903. 



THE SECRETION OF URINE 421 

ered that normal urine contains no albumin, recent work has 
rendered it very probable that traces of albumin, as well as of 
sugar, are normally present in this secretion. 11 In order to 
demonstrate this trace of albumin, however, it is necessary to 
make use of special methods, such as the concentration of the 
large quantities of urine. This albumin is believed by Senator 
and Morner to be derived from the blood by a process of filtra- 
tion through the glomeruli. Owing to the presence of chon- 
droidin-sulphuric or nucleinic acids in the urine, this albumin 
may be precipitated by adding acetic acid. One should there- 
fore be cautious and not conclude too hastily that the precipi- 
tate that so often results from the addition of acetic acid to 
urine is necessarily due to mucin or nucleo-albumin, derived 
from the cells of the kidneys or urinary passages. The urine 
may, however, contain true mucin, which is free of phospho- 
rus and which is derived from the epithelium of the urinary 
passages. 12 

There are persons who continually or at intervals show 
easily demonstrable quantities of albumin in their urine with- 
out feeling ill in any way. We cannot assume that the kidneys 
of such individuals are absolutely normal, in spite of the fact 
that the ordinary symptoms of chronic nephritis are absent and 
that the affected persons remain, to all appearances, perfectly 
healthy. It is certain that chronic nephritis frequently follows 
quite a different course from that ordinarily described in our 
text-books on medicine, and it is quite possible that many of 
these cases represent exceedingly mild forms of the disease. 

The So-Called Physiological Albuminurias. 13 — Aside from 

11 Posner, Virch. Arch., vol. civ. p. 497; Leube, Ztft. f. klin. Med., 
vol. xiii. p. 1 ; Morner, Skan. Arch. f. Physiol., vol. vi. p. 332. 

13 Morner, loc. cit. ; v. Noordcn, Arch. f. klin. Med., vol. xxxviii. 
p. 204. 

13 Leube, Virch. Arch., vol. lxxii. p. 145, and Ztft. f. klin. Med., vol. 
xiii. p. 1; Ther. d. Gegenw., October, 1902; Zeehuisen, Ztrbl. f. in. Med., 
1896, No. 2. 



422 CLINICAL PATHOLOGY 

the class of cases mentioned in the last paragraph, there is a 
class of so-called physiological albuminurias, in which albumin 
in various quantities is present in the urine transitorily, without 
producing any symptoms. Here again it is often extremely 
difficult to decide whether such conditions are normal or 
whether they may not represent the milder stages of some 
really serious renal disease. 

Among the causes which may lead to the excretion of albu- 
minous urine are violent physical exertion u and cold baths. 15 
It is interesting that the former leads to albuminuria more 
readily in the morning than in the afternoon, and more read- 
ily if the patient be standing than if he be lying, being similar 
in these respects to the so-called albuminuria of adolescence. 
It is possible that excitement causes albumin to appear in the 
urine in some cases. 

In some instances, the taking of food has caused an albu- 
minuria to disappear. 16 On the other hand, albumin may be 
excreted in the urine after the ingestion of food, and especially 
of many raw eggs. 17 It is possible that in these cases the eggs 
cause some intestinal disturbance, that the albumin is directly 
absorbed without being normally digested, and that this ab- 
normal proteid in the blood is then immediately excreted by the 
kidneys. 18 

The Albuminuria of Adolesence. 19 — This form of albu- 
minuria cannot be strictly separated from the preceding. It 
tends to occur during childhood and during the period of 
puberty, especially in weak and anaemic individuals. As a 
rule, the albumin appears in the morning, and exercise, excite- 
ment, or diatetic errors may all favor its appearance. 

"Darling, Boston Med. and Surg. Jour., 1899, p. 231. 

15 Rem-Picci, cit. in Jahresber. f. Thierch., 1901, p. 820. 

16 Edel, Munch, med. Wochens., 1901, Nos. 46 and 47. . 

17 See Neumeister, Physiol. Chem., p. 301. 

18 Ascoli, Munch, med. Wochens., 1902, No. 10. 

19 Lommel, Arch. f. klin. Med., vol. lxxviii. p. 541. 



THE SECRETION OF URINE 423 

In many of these patients the amount of albumin in the 
urine follows a definite diurnal curve. During the night and 
immediately after rising, the urine contains no albumin, but 
during the morning hours the amount rapidly increases, reach- 
ing a maximum in the middle of the forenoon, and then finally 
it gradually diminishes or disappears in the afternoon. This 
diurnal variation may, however, be different in different 
cases. 20 It must be remembered, furthermore, that during 
definite renal disease, as at the termination of an acute nephritis, 
as well as in many forms of chronic nephritis, a very similar 
diurnal variation in the excretion of albumin is present. 

The most important factor that influences the albuminuria 
in these cases is the change from the recumbent to the erect 
posture. Exertion, excitement, dietetic and alcoholic excesses 
also frequently seem to exert an influence, but the degree to 
which they do this seems to vary in individual cases. Many 
facts would seem to indicate that circulatory changes cause this 
form of albuminuria, though what the nature of these changes 
is still remains very uncertain. (When a normal individual 
changes from the recumbent to the erect posture, it has been 
shown that, although the maximum blood-pressure is increased, 
the difference between the maximum and the minimum press- 
ures, the so-called pulse-pressure (see page 109) is dimin- 
ished. This diminution in the pulse-pressure is accompanied 
by a lessened secretion of urine in normal individuals and in 
one patient, at least, who had a physiological albuminuria, 
it was regularly accompanied by an increased elimination of 
albumin. This increase also occurred when the pulse-pressure 
was lessened by some other causes. 21 — Ed.) 

The form of albumin excreted by these patients is, in part, 
at least, ordinary serum albumin, and, in part, it is in a form 

20 Weidenfeld, Wien. med. Wochens., 1894, Nos. 12 and 14; Ott, Arch, 
f. klin. Med., vol. liii. p. 604. 

n Erlanger and Hooker, Johns Hopkins Hosp. Reports, vol. xii. 



424 CLINICAL PATHOLOGY 

that is precipitated by acetic acid, — i.e., it is possibly a neucleo- 
proteid. It is important to determine the exact nature of this 
proteid, for we might thereby learn something of its origin. 
There are three possible sources of the albumin in the urine. It 
is possible, in the first place, that the albumin is excreted because 
it is of such a character that it cannot be assimilated by the body 
(see page 431 ) ; in the second place, it may appear because the 
renal cells do not hold back the normal proteids of the blood ; 
and in the third place, it may be derived directly from the cells 
of the kidneys or from the cells of the urinary tract. The fact 
that what appears to be a nucleo-proteid is present in the urine 
of these patients is of especial interest, for only rarely is this 
form of albumin found in the urine of patients with genuine 
nephritis. 

Various views have been expressed as to the relationship 
between this form of albuminuria and true nephritis. Some 
have maintained that the two differ only in degree, while others 
regard the two as fundamentally different. 22 The theory that 
this " albuminuria of adolescence" is a peculiar form of 
nephritis is favored by the facts that it is often accompanied 
by casts in the urine, 23 and that an intermittent albuminuria 
occurs not infrequently during the course of a chronic nephritis 
or toward the close of an acute nephritis. Yet these observa- 
tions do not prove conclusively that we are here dealing with a 
true nephritis in the ordinary use of the term, and even the 
presence of casts is of doubtful significance. Of great prac- 
tical importance is the question as to the prognosis of these 
forms of albuminuria. So far as I know, it has not been defi- 
nitely proved that a single case of this form of albuminuria 
has ever become transformed into a true nephritis. I have 
observed a number of such cases myself over long periods of 

22 See v. Noorden, in discussion on Klemperer's Paper, Berl. klin. 
Wochens., 1889, No. 39; v. Leube, Ther. d. Gegenw., October, 1902. 

23 Huger, Johns Hopkins Hosp. Bull., 1902, p. 75. 



THE SECRETION OF URINE 425 

years, and have yet to see such a transformation, and I am 
therefore personaly inclined to regard them as relatively harm- 
less. Yet more time must elapse before the prognosis of this 
form of albuminuria can be definitely settled. (A more serious 
view of this form of albuminuria is taken by Senator, Caspar, 
and others. 24 — Ed.). 

Albuminuria from Injury to the Renal Cells. — An injury 
to the secreting cells of the kidneys may cause the proteid con- 
stituents of these cells to pass into the urine. Such apparently 
is the interpretation that must be placed upon the appearance 
of nucleo-proteids in the urine after certain injuries to the 
renal parenchyma, such as may be caused by a temporary in- 
terference with the blood-supply, or by the toxins of infec- 
tious diseases. 25 The finding of nucleo-proteids in the urine 
in these conditions is of considerable theoretical interest, and 
it would seem to indicate that the renal cells have been dam- 
aged in some special way, for in most cases of ordinary 
nephritis no nucleo-proteids are excreted. 

On the other hand, an injury to the renal cells may lead 
to albuminuria because it renders them abnormally permeable 
to the passage of the proteids of the blood. This abnormal 
permeability must reside either in the renal cells themselves or 
in the basement membranes, for the walls of the capillaries will 
allow proteids to pass through normally. The epithelium of 
the glomeruli appears to be particularly susceptible to agents 
that increase the permeability in this manner; whereas, the 
epithelium of the convoluted tubules are thus affected only 
when the injurious agent is very powerful. 20 It is difficult to 
judge, however, to what extent the latter have become perme- 
able, for the coagulated proteids often seen in the lumina 

"Zentr. f. in. Med., 1905, p. 67. 

24 Pichlcr and Vogt, Ztrbl. f. in. Med., 1894, No. 17; Obermayer, 
Ztrbl. f. in. Med., 1892, No. 1 ; Kosslcr, Bcrl. klin. Wochens., 1895, No. 14. 

20 Ribbert, Nephritis u. Albuminuria, Bonn, 1881 ; Littcn, Ztrbl. f. d. 
med. Wis., 1880, No. 9. 



426 CLINICAL PATHOLOGY 

of these tubules must have come, in part at least, from the 
glomeruli above. 

We do not know the nature of the changes which render 
the epithelial cells permeable for proteids. In many cases of 
albuminuria, no anatomical lesions of the kidney are demon- 
strable, 27 while, on the other hand, granular and even fatty 
degeneration of the cells may be present without any conse- 
quent albuminuria. Some have attached a certain significance 
to a loss of flagella from the cells of the convoluted tubules, yet 
it seems improbable that this should be of much importance, 
for these flagella may also be lost in conditions in which no 
albuminuria has been present. 28 

Albuminuria from Circulatory Disturbances of the Kid- 
neys. — Circulatory disturbances of the kidneys may lead to 
albuminuria if the velocity of blood-flow through them sinks 
below a certain limit. What this limit is, is not definitely 
known, and it seems to be different in different individuals. 
The retarded renal circulation may be due to a number of 
causes, such as obstruction of the renal veins, increase in the 
general venous pressure, spasm of the renal arteries from lead 
colic, tetanus, etc., or an increased pressure within the urinary 
passages, with secondary pressure upon the renal capillaries 
and veins. It seems probable that the retarded circulation 
primarily injures the renal cells, either by failing to supply 
them with sufficient food or by failing to remove properly the 
waste products derived from their metabolic activities. In con- 
firmation of this view that the primary damage is done to the 
parenchyma cells, is the fact that the proteids which first appear 
in the urine after an artificial constriction of the renal vessels 
are nucleo-proteids, probably derived from the renal cells. 29 

"Linen, Ztft. f. klin. Med., vol. i. p. 131; vol. xxii. p. 182; Ribbert, 
loc. cit. ; Cabot, Jour, of Am. Med. Assoc, 1905, p. 837. 
^Lorenz, Ztft. f. klin. Med., vol. xv. p. 500. 
29 Pichler and Vogt, Ztrbl. f. in. Med., 1894, No. 17. 



THE SECRETION OF URINE 427 

Toxic Albuminurias. — It is easy to conceive how poisonous 
substances, circulating in the blood, might injure the epithelial 
cells of the kidney and render them permeable to proteids. 
Such an effect may be produced by metallic poisons, by the 
balsams, etc., as well as by the more complex bacterial and 
other toxins. The various albuminurias that occur during in- 
fectious diseases, 30 as well as those occurring during preg- 
nancy, belong, for the most part, in this category of toxic albu- 
minurias. It is not a great step from these degenerative pro- 
cesses to the true renal inflammations. In the former only the 
parenchyma cells are affected, whereas in the latter the blood- 
vessels and the interstitial tissues are more or less diseased. 
Many poisons, in small doses, will produce degenerations, and 
in long-continued or very large doses, inflammations ; whereas, 
others seem to cause an inflammation from the start. Why 
some should thus effect the epithelium primarily and others 
the interstitial tissue is not known. The poisons that produce 
these toxic albuminurias are usually formed in the body during 
acute infectious processes; and, even in the so-called primary 
forms of nephritis, bacteria have been found in some instances 
in the urine, thus rendering it probable that the nephritis was 
of infectious origin. 31 

According to the opinion of experienced clinicians, nephritis 
may at times develop after exposure to cold, as from a severe 
wetting or from sleeping upon the ground, but as yet no ade- 
quate explanation of the manner in which such a nephritis is 
caused has been given. 

The Varieties of Proteids in the Urine. — Most of the pro- 
teids that appear in the urine during renal diseases come from 
the blood-plasma, though, as we have seen, a small quantity is 
possibly derived from the renal epithelial cells themselves. No 
definite relation exists, however, between the relative amounts 

""Liithjc, Tlicr. & Gegcnw., November, 1903. 

" Mannaberg, Ztft. f. klin. Med., vol. xviii. p. 223. 



428 CLINICAL PATHOLOGY 

of the various proteids in the blood and the relative amounts 
of these same proteids in the urine. Indeed, in some patho- 
logical conditions only one kind of proteid is excreted by the 
kidneys. 32 The difference in the permeability of the kidneys 
to different proteids apparently depends upon the nature of the 
epithelial lesion. 

Since the investigations from Hofmeister's laboratory have 
shown that the globulins of the blood are made up of at least 
two separate substances, interest has arisen as to the amount 
of these two globulins which appear in the urine in various 
pathological conditions. In chronic nephritis and especially in 
chronic interstitial nephritis, only traces of euglobulin may be 
found in the urine ; 33 whereas, in febrile albuminuria, consid- 
erable amounts of this globulin may appear in the urine. 34 
These globulins are the main causes of certain precipitates that 
form when acetic acid is added to some pathological urines. 35 

Although the greater portion of the abnormal proteids in 
the urine may be classified under the group names of albumins 
and globulins, yet it should be remembered that our chemical 
methods are still very imperfect so far as the further subdivi- 
sion of these groups is concerned. Proteids may give precisely 
the same chemical reactions and yet vary enormously in their 
physiological properties, and while the one is possibly a normal 
constituent of the body, and if artificially introduced into the 
circulation, it will be assimilated and do no harm, another 
may be very toxic, or, at any rate, it cannot be assimilated 
and will consequently be excreted in the urine as a useless 
substance. It is hardly possible to avoid the suspicion that 
certain proteids appear in the urine, especially during acute 

32 Werner, Deut. med. Wochens., 1883, No. 40; Calvo, Ztft. f, klin. 
Med., vol. li. p. 502. 

33 Calvo, loc. cit. 

34 Matsumoto, Arch. f. klin. Med., vol. lxxv. p. 398. 

35 Staehelin, Munch, med. Wochens., 1902, No. 34. 



THE SECRETION OF URINE 429 

infectious diseases, because they are of an abnormal character 
and cannot be assimilated in the body (see page 431). 

The Amount of Albumin excreted. — The amount of albu- 
min in the urine depends primarily upon the degree and extent 
of the injury to the secreting cells, and it is largely independent 
of the quantity of urine excreted. In addition it seems to be 
influenced by the same factors which produce the so-called 
physiological albuminurias, — posture, muscular exertion, etc. 

Casts. — The diseased renal epithelium may become perme- 
able to the red and white corpuscles of the blood, and these can 
then pass into the urine. In addition to these blood-cells and 
the desquamated renal cells themselves, pathological urines 
often contain casts of the interiors of the uriniferous tubules. 
These casts are most frequently composed of a hyaline or gran- 
ular material, but they may contain in addition various cells. 
The material composing them has been regarded by some 
authors as fibrin, and parts of it will often give the Weigert 
reaction; yet it is questionable whether this hyaline material 
is true fibrin or not. Two theories as to the formation of casts 
have been advanced. According to the one, they result from 
the coagulation of the constituents of the blood that escape into 
the uriniferous tubules; according to the other, they are de- 
rived more directly from substances present in the renal cells. 30 
Casts often appear in the urine, even when albumin is absent. 

The Effect of Changes in the Composition of the Blood 

The amount of water in the body directly influences the secre- 
tion of urine, and it is well known, for example, that he who 
drinks much will also urinate much. Indeed, excessive drink- 
ing may be the primary cause of certain cases of diabetes 
insipidus, for it is possible to cure some of them by merely lim- 
iting the quantity of fluids taken by mouth. 81 

"See Torok and Pollak, Arch. f. cxp. Path., vol. xxv. p. 87; Liithjc, 
Arch. f. klin. Med., vol. lxxiv. p. 163. 

7 Westphal, Berl. klin. Wochens., [889, No. 35. 



430 CLINICAL PATHOLOGY 

On the other hand, if the water in the body be diminished, 
either because the patient drinks but little or because he loses 
much water by other channels, then the quantity of urine is 
also diminished. We see such a diminution after excessive 
sweating, especially in a dry climate, as well as in many diar- 
rhceal disturbances, such as Asiatic cholera. The exact cause 
of the many variations in the amount of urine, which obviously 
serve to maintain a constant concentration of the blood, is not 
known. 

Many solid substances also tend to increase the urinary 
secretion, among which substances are many of the constitu- 
ents of normal urine. These constituents appear in the urine, 
not in proportion to their concentration in the blood, but in 
proportion as they are present there in greater or less con- 
centration than normal. If present in greater amount than 
normal, they are rapidly excreted; if present in less amount 
than normal, their excretion is greatly diminished. In this 
way the kidney tends to maintain the blood at a constant 
composition, and for this reason, also, the examination of 
the urine often furnishes the physician with valuable evidence 
as to the concentration of any particular substance in the 
blood. 

When any solid is being excreted, it tends to carry a certain 
amount of water along with it into the urine, though the 
amount of water thus carried out differs for different solids. 
Advantage is taken of this fact in the use of certain substances 
as diuretics. We have already described one class of diuretics, 
— viz., those that increase the secretion of urine by improving 
the circulation through the kidneys. The substances now 
under consideration, however, act in a totally different man- 
ner, for they will increase the urine even when the circulation 
and the renal cells are normal. For example, many salts accel- 
erate the flow of urine, apparently because they readily diffuse 
through the renal membrane and carry a large amount of water 



THE SECRETION OF URINE 431 

with them. Yet we cannot deny that these salts may exert 
some direct specific action upon the renal cells, 38 and such a 
direct action has been definitely proved for certain substances, 
such as caffeine. 39 

The relation between different concentrations of dextrose 
in the blood and the appearance. of dextrose in the urine has 
been carefully studied. About o.i to 0.2 per cent, of sugar is 
normally present in the plasma, and only very minute traces are 
present in the urine. If the concentration in the blood exceeds 
0.2 per cent., however, then dextrose appears in the urine 
in comparatively large quantities. We have already mentioned 
that such a hyperglycemia is the cause of the glycosuria of dia- 
betes ; and, from the fact that the epithelium of the convoluted 
tubules undergo glycogenic degeneration in this disease, it 
seems quite probable that they are the cells which secrete the 
sugar, and so tend to maintain the dextrose in the blood at a 
constant concentration. 

We have said that normal kidneys hold back the proteids 
of the blood plasma most carefully. This is not true, however, 
of all proteids that may happen to be present in the blood. Of 
the many that have been artificially introduced into the cir- 
culation, a small number, such as an egg albumin, casein, and 
haemoglobin, immediately pass through into the urine. Even 
when uncoagulated egg albumin is taken by mouth in large 
quantities, some will often be excreted by the kidneys. Now, 
abnormal proteids are certainly formed in the body during 
some pathological processes, and especially during the infec- 
tious diseases, and it seems not improbable that many of the 
albuminurias present in these conditions are due, not to a pri- 
mary injury to the renal structures, but to the elimination of 
abnormal proteids that cannot be assimilated in the body. So, 

M See, for example, J. B. MacCallum, Jour, of Exp. Zool., vol. i. 
p. 179. 

re Schroder, Arch. f. exp. Path., vol. xxii. p. 53. 



432 CLINICAL PATHOLOGY 

too, those proteids sometimes found in the urine during leu- 
kaemia, which are precipitated by the addition of acetic acid, are 
also possibly excreted because they cannot be assimilated. In 
fact, such abnormal proteids have been demonstrated in the 
blood itself. 40 

Albumoses and peptones will also appear in the urine if they 
be injected into the circulation in sufficiently large quantities. 
They do not appear normally during digestion, apparently be- 
cause they are reconverted into more complex proteids in or 
just behind the intestinal mucosa. Possibly this reconvertion 
does not take place under certain pathological conditions, and 
this may explain the albumosurias, occasionally seen in connec- 
tion with ulcerations of the intestinal wall. 41 In other condi- 
tions, as in fever, albumoses are formed during a pathological 
destruction of the proteids of the body, and here again they 
may appear in the urine. 

Living bacteria may be excreted by the apparently intact 
kidneys, and so reach the urine. They can certainly pass 
through the glomeruli in this manner, for micro-organisms 
have been seen within these structures. 

The Effect of Disturbances of the Urinary Secretion upon 
the Body. — Disease of the kidney may effect the body in at 
least two ways, — either by allowing substances to pass out 
which ought to be retained, or by retaining substances which 
ought to pass out. Of the substances that escape abnormally, 
albumin is the only one of importance. The actual loss of pro- 
teids by this channel is, however, relatively slight, amounting 
to only a small number of grams a day. It seems quite im- 
probable that this small loss should in itself produce much effect 
upon the body as a whole, though it cannot be denied that it 
may affect the composition of the blood to some extent (see 
page 175). 

40 Obermayer, Ztfbl. f. in. Med., 1892, No. 1. 

41 Schultess, Arch. f. klin. Med., vol. lviii. p. 325 ; vol. lx. p. 55. 



THE SECRETION OF URINE 433 

On the other hand, the retention of substances in the body 
that should normally be excreted apparently leads to a variety 
of disturbances. 

Uraemia. — Not infrequently, during- the course of renal dis- 
ease, a group of symptoms develops which seems to be caused 
by some sort of an intoxication. This is called uraemia, 42 and 
it presents the most varied clinical picture. The patient may 
become stupid or comatose, or, on the other hand, extremely 
irritable. He may have local or general convulsions, or he may 
suffer from paralysis of various parts of his body. Sometimes 
he becomes blind without there being present any objective 
lesion in the eyes. The heart's action is at first slow and irreg- 
ular, but later very rapid; the respirations become deeper or 
assume the Cheyne-Stokes type; finally, there may be vomit- 
ing or diarrhoea. These are the most important symptoms of 
this condition. They occur singly or in groups, and they may 
develop suddenly or slowly. The greater number of them are 
evidently due to cerebral disturbances, though, as a rule, no 
corresponding anatomical lesions are found there. 

It has recently been claimed that these many and varied 
symptoms do not all arise from a common cause, 43 and I 
am personally inclined to be of this opinion. Yet it is diffi- 
cult to decide this question, for, as is well known, the same 
poison may act quite differently upon different individuals, 
and upon different organs in different individuals, owing to 
variations in the susceptibility of different persons. As we 
shall see, furthermore, there are reasons for believing that 
a number of causes may be operative in the production of 
uraemia. 



43 See Landois, Die Ursemia, second edition ; Bouchard, Legons sur 
les autointox., Paris, 1887; Honigmann, in Lubarsch-Ostertag, Ergeb. d. 
allge. Path. Physiol. ; Ascoli, Vorles. u. Urremie, Jena, 1903 ; Herter, Mon- 
treal mcd. Jour., May, 1898. 

48 Ascoli, loc. cit. 



434 CLINICAL PATHOLOGY 

Beyond doubt, the symptoms of uraemia are caused by 
some sort of an intoxication, and our first supposition would 
naturally be that this intoxication is due to the retention of 
substances in the body that should normally be excreted by 
the kidneys. As a matter of fact, patients in uraemia fre- 
quently excrete abnormally small amounts of urine and of 
urinary solids. 44 Indeed, the excretion of various solids may 
be diminished even though the quantity of urine be increased. 
The retention of urinary substances in the body has, further- 
more, been directly demonstrated by examinations of the blood. 
The number of molecules in the plasma is increased during 
uraemia, for its freezing point is lowered. Since its electrical 
conductivity is unaltered, 45 however, the increased concentra- 
tion of the blood cannot be due to an excess of electrolytes, 
such as salts, but to an excess of organic molecules of some 
sort. 

Yet a number of facts speak against the view that uraemia 
is caused by the retention of substances that are normally 
excreted through the kidneys. In the first place, an abso- 
lute anuria may persist for days without producing uraemic 
symptoms, and. furthermore, even though death results from 
suppression of urine, the associated symptoms do not pre- 
cisely coincide with those of uraemia. Patients with anuria 
seem to pass gradually into a coma without any irritative 
cerebral symptoms, and the uraemic rise in the blood-pres- 
sure, the slow pulse, and the characteristic convulsions are all 
absent. 

Furthermore, no well-defined substance has yet been found 
that is both retained in the body during uraemia and is capable 

"Fleischer. Arch. f. klin. Med., vol. xxix. p. 129; v. Noorden and 
Ritter, Ztft. f. klin. Med., vol. xix. Sup., p, 197; v. Noorden, Path. d. 
Stoffwechsels, p. 360; Soetbeer, Ztft. f. phys. Chem., vol. xxxv. p. 85; 
Kohler, Arch. f. klin. Med., vol. lxv. p. 548. 

45 See Bickel, Deut. med. Wochens., 1902, No. 28. 



THE SECRETION OF URINE 435 

of procuring uraemic symptoms when injected into a normal 
animal. Many such substances have been described, yet not 
one has stood the test of time. Urea, for example, is retained 
in the body during uraemia, 46 yet it is not toxic in these 
amounts, and a similar retention has continued for days with- 
out the appearance of any uraemic symptoms. 47 Some have 
regarded the potassium salts as toxic agents, yet the quantity 
of these salts in the blood of uraemic dogs was not found to be 
increased. 48 The evidence regarding creatin and uric acid in 
their relation to uraemia is likewise very inconclusive. 40 We 
may say, in conclusion, therefore, that no well-defined sub- 
stance is known which will produce uraemia by its retention 
in the body. 

The urine, however, even in health, possesses certain toxic 
properties, the exact cause of which is at present unknown. 50 
The toxic action of the urine is frequently increased in dis- 
ease, and it is quite possible that in nephritis toxic substances 
are formed in abnormally large quantities, and that they are 
not eliminated properly by the kidneys. Yet this is a pure 
hypothesis, built upon very insecure foundations, for but little 
reliance can be placed upon inferences as to the toxicity of 
normal and pathological urines, when the inferences are de- 
rived from the effects of injections of the whole urine into ani- 
mals. Until some definite toxic substance can be isolated, this 
hypothesis will continue to retain a more or less questionable 
standing. 

Finally, there exists the possibility that uraemia is due, not 
to a failure on the part of the kidney to eliminate poisonous 
substances from the body, but to pathological alteration in 

ia Soctbccr, loc. cit. 
" Fleischer, loc. cit. 

"v. Limbeck, Arch. f. exp. Path., vol. xxx. p. 180. 
"Landois, loc. cit.; Bouchard, loc. cit. 

"Bouchard, Autointoxication; -<■'■. also, Honigmann, on Uraemia in 
Lubarsch-Ostertag, vol. viii. p. 549- 



436 CLINICAL PATHOLOGY 

some of its metabolic functions. Of these functions, we know 
comparatively little; yet that the kidney does possess such 
functions is proved by the well-known fact that the renal cells 
can form hippuric acid out of benzoic acid and glycocoll. 51 
Brown-Sequard 52 has elaborated the theory that the kidney 
furnishes an internal secretion to the body, and he has at- 
tempted to explain unemia from this stand-point. Various 
effects are said to follow the injection of renal extracts, 53 and 
it has been found that substances tending to raise the blood- 
pressure are present in normal kidneys, and that they are 
present in especially large quantities in pathological kidneys. 54 
Possibly, further work along these suggestive lines will aid us 
in our understanding of uraemia. 

In conclusion, we may say that although a complete sup- 
pression of urine is fatal, the symptoms produced are not abso- 
lutely identical with those of uraemia. The convulsions, the 
increased blood-pressure, and the slow pulse, all of which occur 
so frequently in uraemia, are in all probability caused, not by 
the retention of normal urinary products, but by some special 
uraemic toxin. This hypothetical toxin acts especially upon 
the central nervous system, and here more particularly upon 
the cerebral cortex and the medullary centres. In either place 
it may produce a stimulation or a paralysis. 

THE URINARY PASSAGES. 

Any portion of the urinary passage, from the kidney out 
to the mouth of the urethra, may be diseased. Diseases of the 
urinary bladder and of the renal pelves stand in close etiolog- 
ical relation to one another. If, for example, one of the 
latter is inflamed, the infected urine that flows into the blad- 

01 Bunge and Schmiederberg, Arch. f. exp. Path., vol. vi. p. 233. 

62 Arch, de Physiol., 1893, p. 778. 

03 Lepine, Revue de med., vol. ix. p. 514. 

"Ascoli, loc. cit, chap, x., xi. 



THE SECRETION OF URINE 437 

der may there cause changes. On the other hand, if the for- 
mer be the seat of an inflammation, this may easily spread 
upward through the ureters to the pelves of the kidneys. Pye- 
litis is most frequently caused by just such an ascending infec- 
tion, and every long-continued cystitis is a menace to the 
patient, for it may produce inflammation of the renal pelvis 
or of the kidney itself. Certain infections, especially tubercu- 
losis, affect the renal pelvis primarily, in which case the infec- 
tion enters through the kidneys. 

Pathological conditions of the urinary bladder may be 
caused by vesical calculi, by the irritative or infectious char- 
acter of the urine that comes from the kidneys, or by inflam- 
mations in the neighborhood that extend into it by contiguity. 
More frequently, however, the infectious agent reaches the 
bladder through the urethra. It is possible that, in some in- 
stances, bacteria enters from the anterior urethra, because the 
sphincters are weakened or paralyzed; but more frequently 
the micro-organisms are directly introduced by a catheter or 
some other instrument. Such an introduction of bacteria into 
the bladder does not necessarily cause an inflammation; for 
the normal, complete evacuation of this organ protects it to a 
certain extent against infection. On the other hand, infection 
is greatly favored by stasis of the urine, and, for this reason, 
hypertrophy of the prostate gland, strictures in the urethra, 
vesical calculi, tumors, etc., are all frequently followed by 
cystitis. 

When bacteria develop in the stagnating contents of the 
bladder, they may cause various urinary decompositions. Of 
these, none is more frequent than the so-called ammoniacal 
decomposition, in which a portion of the urea is transformed 
into ammonium carbonate, and which may be brought about 
by various bacteria. 5B In other forms of urinary decomposi- 

"Lcube, Virch. Arch., vol. c. p. 540 ; v. Jaksch, Ztft. f. phys. Chem., 
vol. v. p. 395- 



438 CLINICAL PATHOLOGY 

tion the neutral sulphur in the urine is converted into hydro- 
gen sulphide. 50 The effects of such fermentations are both 
general and local. The ammonium salts and the hydro- 
gen sulphide may be absorbed through the altered vesical 
mucous membrane, and produce their general toxic effects. In 
addition to this, the ammonia directly attacks the bladder 
mucosa. 

Urinary Calculi. — Urinary calculi may be composed of 
various compounds, such as uric acid, the urates, calcium 
oxalate, cystin, the carbonates and phosphates of the alka- 
line earths, etc. In addition to one or more of these, the cal- 
culus always contains a framework that is composed of a pro- 
teid-like substance, and this framework is often so intimately 
mixed with the salts present that chemical methods are nec- 
essary to distinguish them. Some stones are of uniform struc- 
ture throughout, while others show a more or less concentric 
arrangement, owing to the fact that layers of one substance 
alternate with layers of another. 

An organic framework is present not alone in formed urin- 
ary calculi, but in urinary crystals of every description. 57 This 
fact is of considerable theoretical interest; and, whereas, it 
was formerly supposed that the organic framework was path- 
ological and was a necessary condition for the formation 
of calculi, it is now regarded as a physiological structure 
and comparatively harmless. The material out of which 
this framework is composed is apparently present in every 
urine, and it is precipitated along with the precipitation of 
the inorganic salts. No special explanation of the pres- 
ence of this organic framework in urinary calculi is therefore 
necessary. 

(a) Uric Acid and Urate Calculi. — The calculi most fre- 
quently found in the bladder are composed of uric acid or of 

50 F. Miiller, Berl. klin. Wochens., 1887, Nos. 23 and 24. 
67 Moritz, Kongr. f. in. Med., 1896, p. 523. 



THE SECRETION OF URINE 439 

the urates. Uric acid stones are often formed in the kidneys 
themselves and apparently even during the earliest periods of 
life. As is well known, uric acid deposits are frequently pres- 
ent in the uriniferous tubules of the foetus and of the new- 
born infant, forming the so-called uric acid infarcts. For our 
present purposes it is immaterial whether the uric acid in these 
cases is excreted in excessive amounts or whether it is merely 
precipitated with unusual ease ; for the formation of calculi de- 
pends primarily upon the precipitation of salts. Apparently 
these renal deposits in new-born infants are normally washed 
out of the kidneys and out of the urinary passages without 
causing any symptoms. Possibly, however, these infarcts 
stand in some close causal relation to the formation of uric 
acid stones in childhood. 

Since the formation of calculi depends primarily upon the 
precipitation of the uric acid out of the urine, two factors 
are of importance in their formation, first, the amount of uric 
acid secreted, and secondly, the ability of the urine to hold this 
in solution. Of these, the latter factor is the more important 
and the more variable. Urine dissolves far more uric acid than 
does pure water. 58 Normally the uric acid is present in the 
urine mainly as a mono-sodium salt. The mono-sodium phos- 
phate of the urine, however, tends to take the sodium away 
from the monourate, forming a di-sodium phosphate and leav- 
ing free uric acid, which latter is comparatively insoluble. 
The presence of free carbonic acid in the urine tends to hold 
uric acid in solution. 69 It is furthermore quite possible that uric 
acid is often held in solution in the urine as some special com- 
bination. We know, for example, that the quantity of urea in 
the urine affects the solubility of uric acid/'" and it is 
probable that other organic substances will do the same. Uric 

"Bungc, Physiol. Chem., third edition, p. 308. 
110 G. EClemperer, /.tit. f. phys. Ther., vol. iv. p. 48. 

°°Rii(lrl, Arch. f. exp. Path., vol. xxx. p. 4'mj. 



440 CLINICAL PATHOLOGY 

acid calculi are often associated with gout, the two being 
grouped together under the name of the uric acid diathesis. 
We have already seen that the uric acid within the body is 
probably held in solution in organic combinations (page 373), 
and the same may be equally true concerning the urine. We 
may say, therefore, in conclusion, that the precipitation of 
uric acid out of the urine depends upon numerous factors, and 
that the presence or absence of other substances probably 
plays a more important role than does the mere quantity of the 
acid itself. 

(b) Oxalate Calculi. — The solution of calcium oxalate in 
the urine is greatly favored by an acid reaction. If this lat- 
ter be reduced from any cause, the mono-sodium phosphate 
tends to be converted into di-sodium phosphate, and the pre- 
cipitation of calcium oxalate is favored; yet this appears to 
be only one factor in the process. 61 

(c) Phosphatic Calculi. — The phosphates of the alkaline 
earths are soluble in the urine mainly as mono- or di-phos- 
phatic salts, and they tend to be precipitated when the reaction 
of the urine becomes alkaline and normal phosphates are 
formed. Ammonium-magnesium-phosphate is also formed 
under these circumstances. 

These phosphatic calculi are formed almost exclusively in 
the bladder, but they frequently precipitate about a nucleus 
composed of some other material, such as a uric acid stone or 
some foreign body that has been artificially introduced into 
the bladder. Their formation is greatly favored by stagna- 
tion of urine, and, as a consequence, they occur most fre- 
quently in association with cystitis; for this, as we have 
shown, is itself favored by stagnation, and is frequently ac- 
companied by an alkaline reaction of the urine, owing to the 
associated ammoniacal fermentation. 

61 G. Klemperer, Berl. klin. Wochens., 1901, p. 1289 ; Klemperer and 
Tritschler, Ztft. f. klin. Med., vol. xliv. p. 337. 



THE SECRETION OF URINE 441 

(d) Cystin and Xanthin calculi are extremely rare. The 
former is a substance containing sulphur, and is derived from 
proteid sources. It appears to be formed by certain little 
understood bacterial decompositions in the intestines. Ap- 
parently, it never occurs in normal urine. Xanthin is present 
even in normal urine in small amounts, but the cause of its 
precipitation is not understood. 

The Symptoms of Urinary Calculi — The hard, uneven 
stones, especially the uric acid or calcium oxalate calculi, irri- 
tate the mucous membrane of the urinary tract and cause in- 
flammations, pain, and hemorrhages. If the calculus obstruct 
a ureter, then attacks of renal colic, with severe pains and 
vomiting, may follow. If the occlusion persists for a long 
period of time, then hydronephrosis and the other sequelae of 
urinary retention are likely to develop. 

Vesical calculi may suddenly stop the flow of urine by 
dropping before the mouth of the urethra. This gives rise 
to vesical tenesmus, which is not, however, a pathognomonic 
symptom of calculi, but may be produced by inflammations of 
the neck of the bladder or by vesical tumors. The symptoms 
of vesical tenesmus are very similar to those of tenesmus of 
the rectum. The irritation of the neck of the bladder causes 
a frequent desire to urinate and the bladder consequently con- 
tracts frequently and forcibly, and this causes considerable 
pain ; yet, on account of the small amount of urine present, 
but little can be voided. 

The Origin of Pain in the Urinary Passages. — A diseased 
kidney may cause pain, or, at any rate, a dull feeling of press- 
ure in the lumbar region. This is not infrequently observed 
in association with acute or chronic nephritis. More severe 
pains are usually due to affections of the lower urinary pas- 
sages, and, as a rule, they are caused by a spasm of the smooth 
muscle lining the urinary tract. These spasms arc caused by 
reflexes from the mucous men ll franc, which originate either 



442 



CLINICAL PATHOLOGY 



from the irritation produced by a foreign body or from in- 
flammatory or ulcerative processes in the mucous membrane 
itself. The muscular spasm in these cases is comparable to 
that which gives rise to biliary or intestinal colic. Ap- 
parently, the mucous membrane possesses nerves of sensation 
and the direct irritation of these may also cause certain 
unpleasant sensations. 



CHAPTER XII. 

THE NERVOUS SYSTEM. 

The activities of the nervous system give rise to two 
classes of phenomena, those pertaining to the body and those 
pertaining to the mind. We do not propose to consider the 
latter, nor even to discuss the relationship that exists between 
the body and the mind. This question involves some of the 
deepest problems concerning life, and psychiatry must assist 
psychology in their solution ; for in this as in other fields of 
medicine, our knowledge of the normal physiological pro- 
cesses becomes broader and more accurate when we study the 
pathological variations that these processes may undergo. In 
the present chapter we propose to limit our discussion, in a 
general way, to those disturbances of the nervous system 
which do not affect the mind, even though this division is an 
artificial one and cannot be carried out strictly and con- 
sistently. 

The nervous symptoms that we propose to consider may 
be divided into two main groups. Those in the first group 
are called focal symptoms, because they are caused by patho- 
logical changes involving certain limited portions of the ner- 
vous system. Those in the second group are called general 
symptoms because the agent that causes them affects the ner- 
vous system as a whole. Of these general symptoms, some 
evidently proceed from certain definite localities, whereas the 
origin of many others cannot be traced. The same general 
injurious agent may act upon all parts of the nervous system, 
yet it affects certain portions more than others, because the 
former happen to be more vulnerable to the particular agent 
in question. 

Disturbances of the Circulation. — The central nervous 

443 



444 CLINICAL PATHOLOGY 

system must receive a sufficient supply of blood in order to 
function properly. Some of the symptoms that result from 
circulatory disturbances have already been mentioned in the 
chapter on respiration. We spoke there of the extraordinary 
sensitiveness of the respiratory centre to any change in the 
quantity or quality of the blood that comes to it, as well as of 
the effects of such changes upon other medullary centres. The 
cerebral cortex is not affected until some time after the 
medulla, at which time the consciousness becomes clouded and 
the horrible sense of suffocation is diminished or lost. Al- 
though the brain is ordinarily extremely sensitive to circula- 
tory changes, it often appears as if it can accommodate itself 
to an insufficient blood supply in chronic circulatory derange- 
ments. It is extremely difficult, however, to form an accurate 
judgment on this question, for we have no method for meas- 
uring the circulatory disturbances in the brain ; yet it is often 
truly astonishing to see what little effect the most pronounced 
chronic venous stasis or the most marked arterial anaemia pro- 
duces upon the cerebral functions. 

The temporary loss of consciousness known as fainting is 
usually due to an acute cerebral anaemia. It may occur in 
strong and otherwise healthy individuals, but it is much 
more frequent in anaemic girls or in older individuals with 
degenerations of the cerebral arteries. During the fainting 
spell the patient loses consciousness, falls, and lies for a time, 
breathing quietly, but with a pale, non-cyanosed face. Finally, 
after a while, he gradually recovers. Although the cerebrum 
has ceased to act, the medulla appears to perform its functions 
quite normally, just as it does during light narcosis. It seems 
improbable, therefore, that the disturbance of circulation in 
fainting affects all parts of the brain equally ; for if this were 
so, we should expect more medullary symptoms. We know 
that localized anaemias frequently occur in other parts of the 
body, and that, in arteriosclerosis, such circumscribed circula- 



THE NERVOUS SYSTEM 445 

tory derangements are particularly frequent; and it seems 
quite possible that the anaemia causing the syncope affects only 
a part of the brain, as could happen, for example, if certain 
vessels became narrowed either by a spasm or by a relative 
thickening of their vails. 

Other anaemic manifestations of nervous origin are more 
difficult to explain. Some, such as headache, ringing in the 
ears, spots before the eyes, and dizziness, appear to be irrita- 
tive in character; while others, such as the common feeling 
of lassitude, are depressive. These symptoms are often 
ascribed directly to a cerebral anaemia which either diminishes 
the oxygen supply to the brain or affects its nutrition in some 
other way ; but these suppositions have not yet been definitely 
proved. There are many other possibilities. Chemical sub- 
stances, resulting from pathological alterations of the general 
metabolism, may poison the brain in some manner, and it is 
even possible that the symptoms do not originate in the brain 
at all, but in the peripheral sense organs. Finally, Lenhartz x 
has shown that the headache and dizziness of chlorosis are 
associated with an increase in the subarachnoid pressure. It 
is apparent, therefore, that the general nervous symptoms of 
anaemia may arise from a variety of causes. 

The Cerebrospinal Lymphatic System. — The brain and 
spinal cord are suspended in a fluid that is constantly changing 
through the processes of secretion and absorption. We need 
not describe the many advantages of this mechanism; how 
it acts as a cushion about the delicate nervous structures when 
the body is jarred, nor how the brain is protected from rapid 
alterations in arterial pressure by the layer of lymphatic fluid 
that circles each of its blood-vessels. 

Most observers have found the pressure of the cerebro- 
spinal fluid to be normally rather low, although it apparently 
differs considerably in different individuals. Us height depends 

1 Munch, mod. Wochcns., 1896, Nos. 8 and 9. 



446 CLINICAL PATHOLOGY 

in part upon the general blood-pressure, but mainly upon 
the relation that exists between the secretion and the absorp- 
tion of the lymph. The characteristic composition of this 
cerebrospinal fluid — viz., a low percentage of albumin and a 
high percentage of potassium salts — shows that it is not an or- 
dinary transudate, but a secretory product from certain cells, 
probably those of the choroid plexuses. 2 The resorption of 
this fluid takes place mainly in the Pacchionian corpuscles and 
to a lesser extent in the lymphatics of the nose and neck. 

Increased Cerebral Pressure. — The pressure of the cere- 
brospinal fluid may be pathologically increased to varying de- 
grees and by different causes. For example, tumors may 
bring this about merely because they take up space within the 
cranial cavity, though they are especially liable to do so when 
they press upon the veins of Galen and thus impede the out- 
flow of venous blood. Intracranial hemorrhages may also 
increase the cerebrospinal pressure. 

If the cranial cavity becomes crowded from any cause, the 
brain substance cannot be compressed into a smaller space, for 
the nervous tissue is practically incompressible. 3 A certain 
relief is afforded, however, by the escape of cerebrospinal fluid 
into those portions of the dura mater that are comparatively 
distensible, such as is the dura of the cord. A new equili- 
brium of pressure is then established. What the new pressure 
will be depends upon the size of the compressing agent, the 
distensibility of the dura, and, finally, upon the relation that 
exists between the secretion and absorption of cerebrospinal 
fluid. It is apparent that when so many factors enter into the 
final result the same cause may produce quite different effects 
in different individuals. 

From these considerations it would appear that, when a 
hard body is added to the contents of the skull, the increase in 

2 Falkenheim and Naunyn, Arch. f. exp. Path., vol. xxii. p. 269. 
8 Grashey, Allgem. Ztft. f. Psych., vol. xliii. p. 267. 



THE NERVOUS SYSTEM 447 

pressure would be roughly proportionate to the size of the 
" foreign body," and that the space taken up by smaller bodies 
could be fairly well compensated for by the escape of lymph 
from the cranial cavity. In certain cases, however, especially 
in certain brain tumors, no such definite relation seems to exist 
between the size of the tumor and the increase in the cerebro- 
spinal pressure. The smallest tumor may cause a tremendous 
rise in pressure. Furthermore, if some of the cerebrospinal 
fluid be drawn off in order to relieve the pressure, it will fre- 
quently re-collect with great rapidity. These facts do not 
accord with the view that brain tumors increase the cerebral 
pressure solely by their mechanical action. It would seem rather 
as if the production or the absorption of the cerebrospinal fluid 
were directly affected. Possibly the conditions present are 
analogous to those that exist in tumors of the pleura or of the 
peritoneum ; i.e., some sort of an inflammatory process is 
taking place in the arachnoid. In favor of this view are the 
facts that the cerebrospinal fluid of these patients often con- 
tains more albumin than normally, and that the accompanying 
choked disk is almost certainly of an inflammatory nature. 

The increased cerebral pressure that accompanies menin- 
gitis is caused by a disturbance in the balance between the pro- 
duction and absorption of cerebrospinal fluid. It seems prob- 
able, indeed, that both the production is increased and the 
absorption diminished in this condition. 

The chronic hydrocephalus of children is characterized by 
a large collection of cerebrospinal fluid, but its cause is not 
well understood. Perhaps a mild inflammatory process is 
present (ependymitis) ; though this seems improbable in most 
cases, from the fact that the percentage of albumin in the 
fluid is not increased. Chlorotic girls frequently show an in- 
creased cerebral pressure, yet here again the cause is very 
uncertain. The mild optic neuritis often seen in these patients 4 

4 Romberg, Bcrl. klin. Wochcns., 1897, No. 25. 



448 CLINICAL PATHOLOGY 

may possibly be produced by the increased cerebral pressure, 
though it seems more probable that it results directly from 
the poor condition of the blood. 

When the pressure of the cerebrospinal fluid is increased 
from any of these causes, certain symptoms usually follow, 
among which are headache, general bodily and psychic weak- 
ness, and characteristic alterations in the fundus of the eyes, 
the so-called choked disks. These have been termed the symp- 
toms of latent cerebral pressure, and they are supposed to be 
caused by the tissue changes that follow the increased pressure 
in the cranial cavity. They depend less upon the height than 
upon the duration of the increased pressure. 5 It would be 
interesting to know what the minimum pressure is that can 
produce a choked disk, but the data at our disposal do not 
suffice to determine this. 6 

Although choked disk is one of the most important clinical 
signs of increased cerebral pressure, the manner in which it is 
produced is still very uncertain. According to the opinion of 
most ophthalmologists, a mere increase in the intracranial 
pressure does not suffice to cause it, and other factors must 
be present. Anatomically, it usually appears to be a true in- 
flammation, involving both the nerve and the neighboring 
retina. 7 The optic papilla is swollen, and there is an asso- 
ciated oedema and venous stasis, but we do not know whether 
the cedema and stasis ordinarily develop before the inflamma- 
tion or not. That stasis alone should cause the inflammation 
is contrary to all our pathological experience with cedema in 
other parts of the body. It is quite possible that some inflam- 

5 Falkenheim and Naunyn, Arch. f. exp. Path., vol. xxii. p. 301. 

8 See Lehnhartz, Munch, med. Wochens., 1896, Nos. 8 and 9; Stadle- 
mann, Grenzgebeite, vol. ii. p. 549. 

7 This is not an invariable rule, however, for Kruckmann has stated in 
a letter to the author that he has recently seen a choked disk that presented 
none of the classical signs of inflammation, this observation being con- 
firmed by Marchand. 



THE NERVOUS SYSTEM 449 

matory irritant, produced by the changes within the brain, 
acts upon the retina. According to this view, two factors 
contribute to the causation of choked disk; first, an increase 
in the pressure of the fluid within the optic sheath; and sec- 
ondly, some unknown inflammatory agent. This hypothesis 
would explain many peculiar cases in which a choked disk 
is absent even though the intracranial pressure is high, as 
happens in some cases of hydrocephalus. It would appear that 
the inflammatory factor is here absent. 

If the pressure of the cerebrospinal fluid be still further in- 
creased, a second series of phenomena develop, the so-called 
direct or manifest symptoms of cerebral pressure. The essen- 
tial causes of these is a disturbance of the cerebral circulation. 
We have already described the peculiar conditions that gov- 
ern the intracranial pressure and how space may be made for 
foreign bodies by an escape of lymph. When, in spite of this 
compensatory mechanism, the pressure attains a certain height, 
those parts of the vascular system that can be compressed most 
easily — i.e., the veins just before their entrance into the rigid 
sinuses — become narrowed or even closed. The resulting sta- 
sis of blood increases the pressure in the corresponding capil- 
laries and the veins are then opened again, so that they alter- 
nately open and close, or, as Grashey says, they vibrate. It is 
not certain what cerebral manifestations accompany this phe- 
nomenon. From experimental data, it would appear that the 
really characteristic symptoms of cerebral compression only 
begin at about the time when the intracranial pressure be- 
comes sufficient to compress the arteries. It is about at this 
time that we have the characteristic stupor, the vomiting, the 
slowing of the pulse and the respirations, and finally the gen- 
eral epileptiform convulsions. The primary cause of these 
symptoms seems to be an arterial anaemia that occurs because 
the subarachnoid pressure is greater than the arterial pressure. 
It is therefore theoretically possible that these symptoms could 

29 



450 CLINICAL PATHOLOGY 

be produced either by a rise in the subarachnoid pressure or 
by a fall in the arterial pressure. When the nervous symptoms 
of increased cerebral pressure have once become established, 
they may continue for some time, even though the intracranial 
pressure lessens, for the reason that less force is required to 
hold the vessels closed than to compress them originally. 

The absolute amount of cerebral pressure necessary to pro- 
duce these direct symptoms is therefore rather indefinite, and 
it often happens that during the course of indirect symptoms, 
the direct ones will appear and again disappear, apparently 
on account of circulatory disturbances. 

(It is a well-recognized fact that, if the space in the cranial 
cavity be rapidly encroached upon by any cause, the general 
blood-pressure is increased. Experiments upon dogs would 
seem to indicate that this rise in the blood-pressure is a pur- 
poseful reaction, and that it serves to keep the pressure within 
the arterioles and capillaries of the medulla at a higher level 
than is the extravascular pressure at this point. In this man- 
ner, a fatal bulbar ansemia, which would otherwise result from 
the rise of intracranial pressure, is warded off. 8 A similar 
rise of blood-pressure has been demonstrated after cerebral 
hemorrhages in man, the extent of the rise being a measure of 
the amount of compression exerted upon the medulla. 9 

At the height of the acute compression, rhythmical breath- 
ing of the Cheyne-Stokes type, rhythmic alterations in the 
size of the pupils, and rhythmic changes in the depth of stupor 
may all occur. These seem to be caused by the varying rela- 
tions between the intracranial and the arterial pressure. 

A final stage of acute cerebral compression has been de- 
scribed, the so-called stage of paralysis, in which the vaso- 
motor centre is no longer able to maintain the arterial pressure 

8 Cushing, Mitth. aus der Grenzgeb., vol. ix. p. 773 ; Am. Jour, of the 
Med. Sci., 1902, vol. lxxiv. p. 375. 

" Cushing, Am. Jour, of the Med. Sci., June, 1903. 



THE NERVOUS SYSTEM 451 

above that in the cranial cavity. The blood-pressure then falls 
rapidly, the heart action and the respirations become irregular, 
the muscles relax, and the deepening coma ends in death. — 
Ed.) 

Cerebral Concussion. — The symptoms of cerebral concus- 
sion differ considerably from those of compression. The pale, 
unconscious patient lies with relaxed muscles and with weak 
respirations. His pulse is soft and small, its rate being either 
increased or diminished. His pupils are often immobile,, and 
vomiting frequently occurs. Indeed, he might be thought to 
be suffering from a fainting spell. 

Cerebral concussion is ordinarily produced by a violent 
blow upon the head or upon some other part of the body, 
yet no definite relation seems to exist between the force of the 
blow and the severity of the symptoms, and even serious cere- 
bral injuries may be produced by violence without there being 
present any of the typical symptoms of concussion. The symp- 
toms of concussion are essentially those of cerebral inactivity, 
reaching different grades in different cases. In the milder 
form of concussion, the cerebral cortex alone is affected (un- 
consciousness), in the more severe forms the medullary centres 
become involved (respiratory and circulatory disturbances), 
while in the most severe the vital functions are suspended. 

No definite anatomical changes in the brain, common to all 
cases of concussion, have been found. The symptoms can 
hardly be due to circulatory disturbances, for they have been 
produced on bloodless frogs. 10 It seems quite probable that 
they are produced by injuries to the finer connections between 
the nerve-cells in the brain, and we know that very severe 
concussions may even produce slight but demonstrable lesions 
in the central nervous system. 11 

'" Koch and Filehne, Arch. f. klin. Chir., vol. xvii. p. 190. 
11 Sclunaus, Virch. Arch., vol. exxii. pp. 326, 470; Kirchgiisscr, Ztft. f. 
Nervcnhcilk, vol. xi. p. 406; vol. xiii. p. 422. 



452 CLINICAL PATHOLOGY 

Disturbances of Motility. — The direct motor impulses 
travel from the cerebrum to the muscles through two sets of 
fibres. Of these, the first begin in the ganglion cells of the 
cortical motor area and pass by way of the pyramidal tracts 
to the anterior horn cells of the spinal cord, or to the corre- 
sponding nuclei of the pons or medulla. The terminal fibres 
of these upper neurons are believed by many to merely touch 
the lower ganglion cells, by others they are believed to be con- 
tinuous with them. 12 The second or lower set of neurons 
begin in the large motor cells of the cord and medulla, and 
extend thence to the peripheral muscles. The voluntary ner- 
vous impulse proceeding to the muscles may be interfered with 
at any point along this long course with a resulting loss of 
muscular function. Disturbances of motility may arise, how- 
ever, from other causes, such as lesions of the muscles, bones, 
and joints, on the one hand, and from lesions of those parts 
of the nervous apparatus that assist in co-ordinating the move- 
ments or that furnish the will power, on the other. 

Some hold that the voluntary motor impulses pass through 
the cerebellum. However this may be, diseases of the cere- 
bellum certainly do influence our voluntary movements, 13 in- 
dependently of their effect upon our sense of equilibrium. The 
innervation of muscles is greatly affected by the centripetal 
impulses that go from them to the brain. These centripetal 
impulses pass through the cerebellum so that cerebellar dis- 
ease at times gives rise to typical ataxia, without there being 
necessarily any disturbances of cutaneous sensation. Since 
the fibres from the cerebellum to the cerebrum undergo decus- 
sation, and since the impulses from the cerebrum to the muscles 
again cross the median line, a unilateral lesion of the cerebel- 
lum will interfere with the movements of the muscles on the 

12 Bethe, Allgem. Anat. f. Path. d. Nervensystem, Leipzig, 1903. 

13 Mann, Monatschr. f. Phys. u. Neur., vol. xii. p. 280; Bruns, Berl. 
klin. Wochens., 1900, Nos. 25 and 26. 



THE NERVOUS SYSTEM 453 

corresponding side of the body, and this interference may be 
so marked as to cause a true cerebellar hemiplegia. 

If a person is unable to move a certain group of muscles, 
we speak of it as a paralysis. If the strength of the movement 
is merely weakened, we speak of it as a paresis. Finally, if 
the movements are uncertain and irregular, so that a desired 
movement cannot be accurately carried out, we speak of it as 
an ataxia. 

(a) "Psychical Paralyses." — This class comprises many 
of the motor disturbances that occur in insane patients, 
especially during stupor, as well as many of the hysterical 
paralyses. It hardly lies within the province of this book to 
discuss the nature of these cases, although the subject is an 
extremely interesting one. It would be necessary to consider 
the nature of the will and the relation that sensations, con- 
ceptions, and memory bear to it, and then, finally, to consider 
the manner in which these relations may be disturbed in the 
various pathological conditions under consideration. 14 

Such " psychical paralyses" are characterized, clinically, 
mainly by their distribution. We do not will a single muscle 
to contract, but we will a certain movement to take place, 
which movement ordinarily involves the use of numerous 
muscles. Correspondingly, the paralyses now under consid- 
eration do not affect single muscles, but they involve whole 
extremities or the execution of certain movements. For exam- 
ple, a patient may be able to move his legs in every direction 
without any incoordination, and yet he may be unable to walk. 
Or he may be able to execute all ordinary movements with his 
hand, but yet be unable to write. 

(b) Prom Lesions of the Motor Tracts. — The ganglion 
cells of the upper motor neurons are situated in the so-called 
motor area of the cerebral cortex, and the symptoms that 

"See Mobius, Ztrbl. f. Nervenh., vol. xi. p. 3; Biswanger, in the 
Nothnagel System ; Krelil, Volkmann's Vortr., N. F., No. 330. 



454 CLINICAL PATHOLOGY 

result from an injury to this part of the brain depends upon the 
portion of the motor area that is affected. The axis cylinders 
of these cells may be injured at any point between their origin 
and their final termination about the large motor cells of the 
cord or medulla. The effect of an injury to this motor tract 
depends, both upon which nerve-fibres are injured and upon 
the severity of the injury. The motor fibres seem to be more 
susceptible to pressure and stretching than are the sensory 
fibres. Injuries to this upper tract are caused most commonly 
by tumors, inflammations, and hemorrhages. The ganglion 
cells in the cord or their processes in the nerves may be af- 
fected by metallic poisons, such as lead, by the action of micro- 
organisms or toxins, as in meningitis, myelitis, and neuritis, 
or finally by disturbances of the blood-supply. 

(c) From Lesions of the Muscles. — Diseases of the mus- 
cles naturally interfere with their functional capabilities, as 
examples of which we may mention the muscular disability 
which accompanies the dystrophies, trichinosis, polymyositis, 
and the parenchymatous degenerations that follow some acute 
infectious diseases. 

(d) From Vascular Disturbances. — Disturbances of the 
blood-supply to muscles may also interfere with their capa- 
bilities. Veterinarians have long known that arterial disease 
in the legs of horses seriously interferes with their powers of 
locomotion. The same is true of man, and the resulting " in- 
termittent claudication" is apparently much more frequent 
than is generally supposed. 15 If the arteries supplying an 
extremity become very narrow, the quantity of blood that 
reaches this extremity may be sufficient to meet all ordinary 
needs, but at the same time it may be insufficient for any ex- 
traordinary demands. When the patient walks, therefore, the 
increased demands of the muscles for fresh blood cannot be 

15 Erb, Ztft. f. Nervenheilk., vol. xiii. p. i ; Munch, med. Wochens., 
1904, p. 905. 



THE NERVOUS SYSTEM 455 

supplied, and, after a certain distance, the leg becomes fa- 
tigued and painful, so that the patient can walk no farther. If 
he rests, however, the power gradually returns and the pains 
leave his legs, because the supply of blood is now again 
sufficient. These characteristic symptoms of intermittent 
claudication are usually associated with definite anatomical 
alterations in the vessels of the affected extremities, which 
alterations usually consist in an obliterating endarteritis. Not 
infrequently these vascular changes eventually lead to gan- 
grene. Apparently a similar intermittent disturbance of func- 
tion may also be caused by a functional, spasmodic narrowing 
of the arteries from nervous causes. 16 The parallelism be- 
tween intermittent claudication and angina pectoris is, there- 
fore, rather striking, for both are usually associated with 
arteriosclerosis, but both may apparently be caused by a ner- 
vous spasm of the corresponding arteries. 

(e) Myotonia Congenita. — The members of certain fam- 
ilies, from youth on, are unable to relax their muscles nor- 
mally after contraction, because the muscle remains in a sort 
of tetanus. This rigidity is most pronounced after a period 
of rest, but, as a rule, it lessens after each repetition of the 
movement. The muscles themselves are usually quite strong, 
even more so than normally. We may infer that the cause of 
the disability is located in the muscle itself, for its reaction to 
the electric current is abnormal (Erb's myotonic reaction), 
and its anatomical structure is also considerably altered. 17 

(/) Asthenic Bulbar Paralysis. 18 — This disease is charac- 
terized clinically by the ease with which certain muscles become 
fatigued alter comparatively slight exertion. This fatigue 
occurs after voluntary use of the muscles, as well as after 

" Oppcnheim, Ztft. f. Nervenheilk., vol. xvii. p. 317. 
" Erb, Die Thomsensche Krankheit, 1886. 

"Jolly, Berl. klin. Wochens., 1895, No. 1; Strumpell, Ztft f. Nervenh., 
vol. viii. p. 16. 



456 CLINICAL PATHOLOGY 

stimulation by the electric current, but the ease with which the 
fatigue develops seems to vary from time to time. Certain 
muscles, especially those supplied from the medulla, tend espe- 
cially to be affected. This disease affects the motor apparatus, 
yet the exact point affected is not known, for anatomical in- 
vestigations have thus far failed to show any lesion. 19 

Disturbances of Co-ordination. 20 — Before we proceed 
to the discussion of disturbances of co-ordination, it is first 
necessary to consider the mechanism whereby we normally 
govern our movements, so that they shall be executed in a 
precise and exact manner. The consideration of the normal 
mechanism of co-ordination presents certain difficulties, how- 
ever, for we are not certain that it is the same in every case. 
The adult executes many movements at will, whereas there 
are others that he learns only by practice. Of the latter, some, 
such as piano-playing, are learned only by certain individuals, 
while others, such as walking, speaking, and writing, are 
learned by all men; such learning being facilitatedj doubt- 
lessly, by the fact that our forefathers have practised these 
movements for generations. There is a gradual transition 
from the movements that must be learned to the purely vol- 
untary movements, and from these voluntary movements 
again there is a gradual transition to the purely involuntary 
movements. To this second transitory class belong those move- 
ments of a reflex or automatic type, such as breathing and 
suckling, that are executed from birth on. As an illustration 
of the difficulty encountered in attempting to separate these 
different classes of movements, we may cite the fact that, while 
swimming must be learned by man, many animals can swim 
when they first enter the water. 

19 Striimpell, Ztft. f. Nervenh., vol. viii. p. 16. 

20 Frenkel, Die Behandlung des tabetischen Ataxie, Leipzig, 1900, trans- 
lated into English by Freyberger ; Forster, Die Physiol, u. Path. d. Koor- 
dination, Jena, 1902. 



THE NERVOUS SYSTEM 457 

There are, therefore, all grades of transition, from the pure 
reflex movements to the most complex volitional acts. Indeed, 
the transition occurs many times in the life of a single indi- 
vidual, for movements that were once learned only with the 
utmost attention and volition are ultimately executed almost 
unconsciously, merely by willing to do them. At first, these 
complex acts are carried out under the conscious guidance of 
all our senses, particularly those of sight, touch, position, etc., 
but by practice they come to be executed without the individual 
constituent movements of the act coming to our consciousness. 

'We know something about the nervous mechanism that 
underlies these complex practised movements and the more 
complicated reflexes. These movements may be set in motion 
voluntarily, or by nervous impulses from the periphery, or, 
finally, by little-understood internal chemical changes. Since 
the resulting movements are varied more or less to suit the 
occasion, it seems improbable that they should be guided by a 
completely developed mechanism lying within the central ner- 
vous system. It would appear rather as if they were guided 
by impulses from the periphery, which supposition receives 
strong support from the experiments that have been performed 
on frogs, dogs, and monkeys. 21 If the posterior nerve-roots 
in these animals be cut, — i.e., if the sensory impulses from the 
periphery be eliminated, — not only the complicated reflexes, 
but the more complex practised movements, such as jumping 
and running, can no longer be carried out as the animal wills, 
with exactness and precision. Some muscles contract too 
strongly, others too feebly, and still others at the wrong time, 
so that the resulting movement, as a whole, loses its precision, 
and the picture is very similar to that seen in certain nervous 
diseases that occur in man, especially tabes. 

Since an electrical stimulation of the motor region of the 

21 H. E. Hering, Arch. f. exp. Path., vol. xxxviii. p. 266; Neurol. Cen- 
tralbl., 1897, No. 23; Prag. med. Wochens., 1896. 



458 CLINICAL PATHOLOGY 

cerebral cortex gives rise to movements, not of individual 
muscles, but of co-ordinated groups of muscles, we are led 
to infer that, in the cortex, movements and not individual mus- 
cles are represented. 22 A further grouping of muscles for the 
execution of certain movements occurs in the anterior horn 
cells of the spinal cord and in the root-fibres. It is quite cer- 
tain, therefore, that a certain degree of co-ordination is derived 
from this arrangement of the cells in the motor nervous sys- 
tem, though, as we have seen, this grouping is not sufficient 
for complex acts. For these, we depend more or less upon 
peripheral sensory impulses. We may or we may not be con- 
scious of these impulses, and even when we are not conscious 
of them, they may yet be utilized by the lower centres in the 
mechanism of co-ordination. These two forms of sensation, 
conscious and unconscious, cannot be strictly separated from 
each other, for our consciousness of them depends largely 
upon the attention that we direct to them. 

Many varieties of sensation may affect our movements. 
Of these, we may name the senses of sight and of hearing, 
those of pressure upon the skin, muscles, tendons, and joints, 
and, finally, the senses of position and of motion. Some of 
these are of greater importance than are others, and we have 
seen, for example, that the senses of sight and of hearing are 
alone inadequate in the monkey and the dog to maintain co- 
ordination during such complex movements as jumping and 
running. 

Of the sensations mentioned, the most important in the 
co-ordination of voluntary movements are those derived from 
the tendons, the joints, and the eyes. 23 If the two former are 
affected in the first interphalangeal joints, for example, then 
even such simple movements as the flexion and extension of the 
fingers may become ataxic. In addition to these sensations 

22 Beevor and Horsley, Philosoph. Trans., vol. clxxxi. p. 129. 

23 Goldscheider, Ztft. f. klin. Med., vol. xv. p. 82. 



THE NERVOUS SYSTEM 459 

from the joints, tendons, and eyes, others from the muscles 
may also play a considerable role in governing our movements. 

While the grouping of muscles according to their use in 
the motor nervous apparatus may therefore furnish a rough 
sort of co-ordination, this is insufficient for the finer move- 
ments. For their execution, centripetal impulses from the 
periphery are necessary in order to control the time at which 
the individual muscles shall begin their contractions, the force 
with which they shall contract, and the time during which they 
shall remain contracted. 

After this preliminary discussion of the theory of ataxia, it 
remains to inquire to what extent disturbances of sensation 
have been actually found in patients who suffer from ataxia, — 
i.e., from an inability to carry out movements in a precise and 
accurate manner. It is quite certain that ataxia may occur 
without there being any demonstrable diminution in the cu- 
taneous senses of pressure, temperature, or pain. 24 On the 
other hand, it has not been proved that ataxia ever occurs in- 
dependently of all sensory disturbances, and the earlier cases 
that were believed to prove this were not sufficiently investi- 
gated as to the finer losses of sensation in the joints and mus- 
cles. 25 Frenkel, in studying one hundred and fifty cases of 
tabes, failed to find a single instance of ataxia unaccompanied 
by sensory changes, these being mainly in the joints and mus- 
cles. 20 We may say, therefore, that the main cause of tabetic 
ataxia is a deficiency in the impulses proceeding from the joints 
and muscles. That this deficiency may be to a certain extent 
compensated for in other ways, is shown by the reliance which 
ataxic individuals place upon their visual impressions. Pos- 
sibly the absent reflexes, as well as the diminution in muscular 

" Friedreich, Virch., vol. lxviii. p. 168. 

25 See Erb, Neurol. Ztrbl., 1895, No. 2; Vierordt, Berl. klin. Wochens., 
1886, No. 21. 

M Neurol. Ztrbl., 1897, Nos. 15 and 16. 



460 CLINICAL PATHOLOGY 

tonus, also play a not inconsiderable part in the motor dis- 
turbances of tabetics. 27 

We now come to the question as to the effect exercised by 
known disturbances of sensation upon co-ordination. In 
other words, do such disturbances necessarily lead to ataxia? 
Many young, apparently hysterical persons have been observed 
who have shown extensive anaesthesias of the skin and of 
the deeper structures, without, however, exhibiting any true 
ataxia. 28 When they kept their eyes open, their movements 
were perfectly normal, which, as we have seen, is not the case 
when, experimentally, all sensory impulses from an extremity 
are cut off. If these patients closed their eyes, their voluntary 
movements were, indeed, somewhat abnormal, but no true 
ataxia was present. To my mind, however, it is necessary to 
be very cautious in our interpretation of these observations, 
because the sensory disturbances were apparently of an hys- 
terical character. Hysterical disturbances of sensation unques- 
tionably have their seat in the most central part of the nervous 
system ; in the mind itself, so to speak ; and even though these 
patients are not conscious of their sensations, the latter may 
certainly be utilized by the lower centres for co-ordination. In 
no other way can we explain the fact that an hysterical girl, 
with absolute insensibility of her hands, is able to execute the 
most delicate hand-work. Indeed, many hysterical patients do 
not know that they have anaesthesias, mainly because the latter 
do not cause any motor disturbances. It seems probable, there- 
fore, that in the cases cited at the beginning of this paragraph 
the ataxia was absent, because the patients unconsciously util- 
ized the centripetal impulses coming from the extremities. 

Investigations on other forms of complete lack of sensa- 
tion are so few that it is impossible to render a final verdict 

27 See Frenkel, Neurol. Ztrbl., 1896, No. 8. 

28 Striimpell, Arch. f. klin. Med., vol. xxii. p. 332 ; Heyne, ibid., vol. 
xlvii. p. 75; v. Ziemssen, ibid., p. 89. 



THE NERVOUS SYSTEM 461 

concerning the effect that these produce upon co-ordination. 
Striimpell, however, has recently published a case in which a 
complete absence of sensation in the right arm affected the 
movements most seriously. So long as the patient's eyes were 
kept open, the ataxia was comparatively slight, but, as soon as 
they were closed, the incoordination became extreme. 29 

We have shown that centripetal sensory impulses are abso- 
lutely necessary for a proper co-ordination of any complex 
act. The lesion that produces the incoordination, however, 
does not necessarily lie in the peripheral tracts, but it may be 
so situated in the central nervous system that it hinders, in 
some manner, the transmission of impulses across this system, 
as has been shown in a number of cases. 30 Ataxias may, 
therefore, be due to different causes, and the resulting clinical 
picture is not always the same. When we speak of ataxia in 
general, we usually refer to the tabetic type, for that is the 
most common and the best understood form. In this form the 
ataxia is always accompanied by demonstrable sensory 
changes. 

If, from any cause, our movements become more or less 
incoordinated, then we attempt to compensate for the loss of 
peripheral control by directing them through the higher cen- 
tres, very much as does one who is trying for the first time to 
execute a difficult movement. The movement, thus directed, 
is usually performed more slowly and less accurately than is 
an automatically regulated movement. Indeed, it not infre- 
quently happens that when a normal individual attempts to 
execute some difficult feat particularly well, — i.e., when he 
watches each individual movement — the feat is done particu- 
larly badly. This shows the superiority of the automatic regu- 
lation over the volitional. A compensation for losses of cen- 
tripetal control may be developed, however, in another way. 

20 Striimpell, Ztft. f. Ncrvenhcilk., vol. xxiii. p. I. 
""Liithjc, Ztft. f. Ncrvenhcilk., vol. xxii. p. 280. 



462 CLINICAL PATHOLOGY 

When the sensory impulses from the affected extremity are not 
all shut off, then the patient may learn to utilize those that are 
left to a far greater extent than they were ever used previously, 
and so to develop a new automatic regulation. 

Disturbances of sensation may affect the functions of the 
body in other ways than by causing ataxia; 31 and here again 
the loss of certain sensations may be compensated for, to a cer- 
tain extent, by other sensations, and especially by those that 
come from the eyes. For this reason, it frequently happens 
that such disturbances only become manifest when the patient 
closes his eyes. When the sense of touch in the hands is lost, 
the patient is unable to grasp objects properly or to gain an 
idea of the contour of surfaces, unless the eyes follow the 
movements of the hand. If the senses of position and of 
motion are diminished, then all the finer movements that de- 
pend upon the position of the body or of the hand in space are 
not executed accurately except under ocular supervision. The 
deaf-mute, whose semicircular canals are destroyed, becomes 
unsteady so soon as his eyes are closed, just as does the ataxic 
tabetic, etc. 

The Effect upon Motion of Variations in the Reflexes. — 
Although the reflexes have been carefully studied, especially in 
regard to their diagnostic significance, very little attention has 
been paid to the important influence that they exert upon our 
voluntary movements, owing to the effect that they have upon 
the state of contraction of the muscles. In addition to this 
they serve to protect the joints from forcible and sudden 
motions. 32 

It is extremely difficult to estimate the precise injury that 
is caused by an absence of the tendon reflexes, for such ab- 
sence is usually associated either with paralysis or with definite 

81 Exner, Pfluger's Arch., vol. xlviii. p. 592; Striimpell, Ztft. f. Ner- 
venh., vol. xxiii. p. 1. 

22 Sternberg, Die Sehnenreflex, Leipzig, 1893, p. 272. 



THE NERVOUS SYSTEM 463 

sensory changes. When the reflexes are much exaggerated, 
the tension of the muscles is increased to such a degree that 
the slightest irritation will call forth a reflex spasm. With 
every motion, the tendons and ligaments, especially those op- 
posing the movement, are put more or less on the stretch. This 
initiates reflex muscular contractions, which tend especially to 
affect the antagonists of the muscles that are innervated. As 
a result, all movements become stiff, and in very bad cases even 
impossible. This reflex innervation of antagonistic muscles 
may cause such uncertainty of movement that the resulting 
picture resembles true ataxia. 33 

Nervous Disturbances of Urination and Defecation. — 
The reflex acts of urination and defecation are so far under 
the control of the will that, up to a certain limit, we can inhibit 
or initiate their taking place. The nervous impulses running 
from the brain to the lower centres merely prevent or permit 
the peripheral sensory impulses from initiating the reflex act. 

The reflex centres that control defecation and urination 
are not situated in the cord, as has been generally supposed. 
They lie in the sympathetic system. 34 The centripetal im- 
pulses that these centres receive from their corresponding 
organs are, in part, excited by distention of the organ. Yet 
distention is only one of the factors that initiate the reflex, for 
we urinate different amounts at different times, and much less 
when the mucous membrane of the bladder is inflamed or 
when the urine is concentrated, highly acid, and irritating. 

In the new-born infant, urination and defecation are purely 
reflex phenomena. When the centripetal impulses become 
sufficiently strong, the reflex mechanism is set in action and the 
viscus is emptied. Only through careful training does the 
child learn to govern these reflexes and gradually to bring 
them within the normal limits of control. 

M H. E. Hering, Piag. tned. Wochens., 1896. 

84 L. R. Muller. Ztft f. Nervenheilk., vol. xxi. p. 86. 



464 CLINICAL PATHOLOGY 

If the impulses running from the cerebrum to the lower 
centres be interrupted from any cause, then voluntary control 
over evacuation is lost. For a time after these impulses are 
cut off, the bladder remains full and continually overflows 
(incontinence from retention), but gradually it comes to 
empty itself reflexly at intervals, just as it does during in- 
fancy. Since this reflex emptying of the bladder may occur 
even when the lumbar cord is destroyed, the centre lies out- 
side the cord. 35 

Other nervous lesions cause various other disturbances. 
For example, a loss of centripetal impulses from the bladder 
to the reflex centre will lead to a pure retention, and a diminu- 
tion in these impulses will lead to difficulty in passing urine, 
to straining, and to delay in starting the stream. Lesions of 
the motor paths may cause similar disturbances, such as slow 
urination and the retention of urine in consequence of a paresis 
of the detrusor, and continual dribbling in consequence of a 
weakness of the sphincter. Irritative lesions of the tracts that 
connect the cerebrum with the reflex centre may cause retention 
of urine from spasm of the sphincters. Finally, it must be 
remembered that the external sphincter is a voluntary muscle, 
and that when it is paralyzed there may result merely an ina- 
bility to hold the urine when the bladder becomes filled. 

The nervous disturbances of defecation appear to be very 
similar to those of urination. 

Pathological Alterations in the Reflexes. — In a pure reflex, 
the sensory impulse acts immediately upon the motor appa- 
ratus without the intervention of the will. The reflex mech- 
anism consists, therefore, of the sensory apparatus, the motor 
apparatus, and the connection between the two. The latter 
may be situated either in the brain, the spinal cord, or the 
sympathetic system. 

(a) The Deep Re-flexes. — Those reflexes which arise from 

35 L. R. Miiller, loc. cit. 



THE NERVOUS SYSTEM 465 

the tendons, periosteum, or bones, and of which the patellar 
reflex is the best-known example, traverse the spinal cord or 
the subcortical portions of the brain. They are subject to 
many and different influences, which latter may act either 
directly upon the sensory or motor apparatus or, more indi- 
rectly, may tend to inhibit or to further the transference of 
the impulse from the sensory to the motor side of the reflex 
arc. 36 

Even normally there is a great variation in the intensity 
of the reflexes, not only in different individuals, but in the 
same individual at different times, the latter being especially 
true of " nervous" patients. The reflexes tend to be exag- 
gerated during fatigue, as well as in marantic and cachectic 
conditions. They show considerable variations in the infec- 
tious diseases. They usually disappear just before death. 

If the reflex arc be broken at any point, whether in the 
sensory, the motor, or central portion, then the correspond- 
ing reflex is abolished. In the earliest stages of tabes dor- 
salis, for example, the knee-jerks may be absent because that 
part of the cord has degenerated through which the sensory 
portion of the reflex must travel. Even when the reflex is 
absent, however, it is possible that the path is not completely 
blocked, but only sufficiently so to inhibit the reflex taking 
place under ordinary conditions. If such be the case, then a 
cerebral lesion that would normally increase the reflex may 
cause the lost one to return. This has been observed in a 
number of cases. 37 

A disease of the reflex arc, such as a neuritis, at times 
causes an exaggeration of the corresponding reflex. 38 It is 

M Sternberg, Die Sehncnreflex, 1893 ; Jendrassik, Arch. f. klin. Med., 
vol. lii. p. 569; Strumpell, Ztft. f. Nervenheilk., vol. xv. p. 254; Kornilow, 
ibid., vol. xxiii. p. 216. 

" See Sternberg, loc. cit., p. 178. 

M Strumpell and Mobius, Munch, med. Wochens., 1886, No. 34; Stern- 
berg, loc. cit. 

30 



466 CLINICAL PATHOLOGY 

possible that, in these cases, the inflamed sensory nerves show 
an increased irritability or conductivity; though it is also 
possible, as Sternberg believes, that the exaggeration is caused 
by changes in the reflex centre. 

The deep reflexes may be influenced by lesions that lie 
outside of the reflex apparatus itself. The most important of 
these are the lesions which interrupt the passage of impulses 
from the cerebrum, or possibly also from the subcortical cen- 
tres, down to the lower spinal reflex centres. Injuries of this 
character are usually followed by an exaggeration of the deep 
reflexes, and it has been assumed that this results from a 
blocking of the inhibitory influence which the brain is sup- 
posed to exert upon the spinal centres. 39 Yet the correctness 
of this interpretation may justly be questioned, for numerous 
observations have established the fact that the patellar reflexes 
may totally disappear after a complete transverse section of 
the spinal cord. 40 In some such cases, however, the tendon 
reflexes have persisted in spite of the transverse lesion, and 
experiments upon dogs and monkeys have yielded equally con- 
flicting results. In them, a complete section of the cord may 
be followed either by increased or by diminished reflexes. 
Immediately after the operation on these animals, the reflexes 
are usually abolished, but they gradually return after a cer- 
tain length of time. The primary injury itself may possibly 
inhibit them for a time, thus causing their primary disappear- 
ance; but their continued absence in clinical cases cannot be 
accounted for in this manner. Possibly some secondary de- 
generations take place in the fibres of the reflex arc, and these 
account for the continued absence of the reflexes. 



a9 Bickel, Ztft. f. Nervenheilk., vol. xxi. p. 304. 

"Sternberg, loc. cit. ; D. Gerhardt, Ztft. f. Nervenheilk., vol. vi. p. 
127 ; L. Bruns, Arch. f. Psych., vol. xxv. p. 759 ; vol. xxviii. p. 133 ; Nonne, 
ibid., vol. xxxiii. p. 393; Kron, Ztft. f. Nervenheilk., vol. xxii. p. 24; 
Kausch, Grenzgeb., vol. vii. p. 541. 



THE NERVOUS SYSTEM 467 

(b) The Superficial Reflexes. 41 — These reflexes are of a 
more complex character than are the deep reflexes, and their 
nature is less understood. A relatively slight stimulus ap- 
plied to the skin or to a mucous membrane will often elicit a 
relatively strong response, and the resulting movements are 
usually slower and more under the control of the will than 
are the deep reflexes. It is quite possible that the nervous 
path that some of these skin reflexes follow traverses the cere- 
brum, and that this is the reason why they are so often absent 
in the very conditions in which the tendon reflexes are exag- 
gerated. Yet this is very questionable, and the data at our 
disposal do not permit us even to formulate any exact hypothe- 
sis as to the nature of the superficial reflexes. 

Strychnine Poisoning and Tetanus. — The violent muscu- 
lar contractions that characterize these conditions are caused 
by an increased irritability of the cells in the spinal cord. 42 In 
strychnine poisoning, the convulsions are of a purely reflex 
character; i.e., they are excited by sensory impulses from the 
periphery. In tetanus some are of this character, whereas 
others are due to a primary stimulation of the large motor 
cells in the cord. These cells certainly become abnormally irri- 
table in tetanus, and some remarkable anatomical changes in 
them have been described. 43 

The brilliant researches of Meyer and Ransom 44 have 
shown that the tetanus toxin travels from the periphery to the 

41 See Jendrassik, Arch. f. klin. Med., vol. lii. p. 569; Striimpell, Ztft. 
f. Nervenheilk., vol. xv. p. 254. 

" Brunner, Beitr. z. klin. Chir., vol. ix. pp. 83, 269; vol. x. p. 305; vol. 
xii. p. 523; Deut. med. Wochens., 1894, No. 5; Gumprccht, Dent. mcd. 
Wochens., 1895, No. 42; Courmont and Duyon, Arch, de Physiol., vol. 
xxv. p. 64; Goldscheidcr, Ztft. f. klin. Med., vol. xxvi. p. 175. 

43 Goldscheider and Flatau, Fortschrittc, etc., 1897, p. 609; 1898, No. 6; 
Westphal, ibid., No. 13. 

44 H. Meyer, Sitzungsber. d. Gcsell. z. Befor. d. Naturw. in Marburg, 
1902, No. 1 ; Meyer and Ransom, Arch. u. exp. Path., vol. xlix. p. 369. 



468 CLINICAL PATHOLOGY 

spinal cord through the axis cylinders of the nerves, and that it 
cannot attack the cord directly from the blood or lymph. The 
nerves must first be entered. For example, if the tetanus anti- 
toxin be injected into certain nerve-trunks of an animal, and if 
at the same time the toxin be injected into the blood or lymph, 
then the regions corresponding to the nerves that have received 
the antitoxin are not affected during the ensuing tetanus. 
When tetanus toxin is injected directly into the spinal cord, 
the incubation period that elapses before the appearance of 
symptoms is reduced to about two and a half hours. This 
demonstrates that the long incubation period, usually present 
in tetanus, is due to the time consumed by the toxin in travel- 
ling from the periphery to the central structures. 

The tetanus toxin first affects the motor cells of the cord 
in such a way as to irritate them and to cause a tonic spasm of 
the corresponding muscles, which spasm is not of a reflex char- 
acter. The toxin then spreads to neighboring cells, especially 
to the motor cells lying on the opposite side of the cord, with 
resulting convulsions in the same muscles as those first af- 
fected, but on the opposite side of the body. Still later, the 
poison affects the sensory portion of the reflex arc, and we 
then get reflex convulsions; yet only those reflexes are in- 
creased which pass through the affected parts of the cord. 

The sensory nerve-fibres do not seem to be affected by the 
tetanus toxin under ordinary conditions ; yet Mayer and Ran- 
som have shown that if the toxin be injected directly into the 
posterior nerve-roots, the first symptoms of the poisoning are 
attacks of violent pains, the so-called tetanus dolorosus. 

Tetanus in man differs from that produced experimentally 
in animals, inasmuch as the muscles first affected are usually 
those of the jaw, producing the well-known trismus; whereas 
experimentally the convulsions begin in the muscles that corre- 
spond to the point of inoculation. 

Contractures — The bones about a joint are not infre- 



THE NERVOUS SYSTEM 469 

quently held in a more or less fixed position. This may be 
due to a number of causes, such as diseases of the joints, scars 
in the skin or muscles, and changes in the muscles, either 
primary or secondary to nervous lesions. Any of these might 
be termed contractures, but it is customary to limit the use 
of the term to those limitations of motion that follow diseases 
of the muscles or of the nerves. 

(a) Passive Contractures. — If, for any reason, certain 
muscles remain shortened over a long period of time, this 
shortening tends to become permanent, and the movements of 
the joint are then correspondingly limited. This condition is 
spoken of as a passive contracture. Of the causes that may 
lead to such a shortening of the muscles, we may name the 
maintenance of a certain posture for a long time. In this man- 
ner, a drop-foot is not infrequently produced by the pressure 
of the bedclothes during a long illness. When certain groups 
of muscles are weakened or paralyzed, either from disease of 
the muscles themselves or from disease of their nervous connec- 
tions, then the antagonistic muscles, not meeting with the nor- 
mal resistance to their action, tend to move the joint into an 
abnormal position and to hold it there. Whenever the joint 
has been held in a certain position for a long time, it tends to 
be fixed in this position both by the development of adhesions 
about the joint itself and by anatomical alterations in the short- 
ened muscles. Passive contractions have been produced ex- 
perimentally in monkeys by the extirpation of portions of the 
cerebral cortex, and by subsequently keeping the animals in 
such small cages that their movements are very much limited. 45 

(b) Active Contractures. — In active contractures, the 
joints are held in an abnormal position by the tonic contraction 
of certain groups of muscles. Since there is usually an asso- 
ciated increase in the tendon reflexes in these cases, they have 

"H. Munk, Dll Bois' Arch, 1896, p. 564. 



470 CLINICAL PATHOLOGY 

been termed by some, spastic contractures. The cause of the 
muscular spasm which produces the contracture is not always 
clear, and it may not be the same in all cases. As we have 
said, the reflexes are usually exaggerated in active contrac- 
tures, yet not necessarily so, and in some cases they remain 
unaffected. 

When the reflexes are increased, the contractures might 
possibly be caused by a reflex stimulation of certain groups of 
muscles about the joint. To my mind, however, this explana- 
tion is not a very satisfactory one, and it seems very probable 
that, in many cases, at least, the contractures and the exag- 
gerated reflexes are both due to a common cause. 

Mann has given a very plausible explanation of post-hemi- 
plegic contractures. 46 He first calls attention to the fact that 
these contractures affect especially the muscles that are least 
paralyzed. In the complicated innervation that directs every 
voluntary movement, there is apparently not only a stimulation 
of the muscles that produce the movement, but an inhibition 
of the antagonistic muscles. A cerebral disease, therefore, will 
not only paralyze certain muscles, but it will at the same time 
diminish the inhibitory impulses sent to their antagonists. This 
lack of inhibition would explain the contracture in the antago- 
nistic muscles, and Mann's hypothesis accords very well with 
the experimental results of H. E. Hering. 47 In many in- 
stances, irritative processes seem to cause the tonic muscular 
spasm, though it must be admitted that no very sharp line can 
be drawn between an irritation and a diminution of inhibitory 
influences. 

(c) Contractures from Joint Disease. — Two views have 
been advanced as to the cause of the contractures that develop 
in joint diseases. According to the one, the muscle spasm is 

46 Mann, Monatschr. f. Psych, u. Neurol., vol. i. p. 409; vol. iv. pp. 
45. 123. 

47 Pfliiger's Arch., vol. lxx. 



THE NERVOUS SYSTEM 471 

caused reflexly from the joint, owing to a strong stimulation 
of the sensory nerves there. This view is supported by the 
fact that the tendon reflexes are often increased in these con- 
ditions. Personally, however, I am inclined to favor the view 
that the muscle spasm and peculiar posture assumed by these 
patients are both the result of a desire to avoid pain ; though 
it must be admitted that this does not explain the increased 
tendon reflexes. 

(d) Hysterical Contractures. — Hysterical contractures are 
usually, but not always, associated with exaggerated reflexes. 
They would appear to be due in part to this exaggeration ; in 
part, perhaps, to a diminution of the inhibitory control nor- 
mally exercised by the brain over the lower spinal centres. 

Motor Irritative Symptoms, (a) Tremor. — Tremor may 
be defined as a series of regular oscillatory muscular move- 
ments about a fixed axis. The rate of these oscillations, their 
amplitude, and the number of muscles affected, all vary in in- 
dividual cases. In many conditions the tremor only occurs 
during voluntary movements; in others, it is more intense 
during rest. All forms of tremor cease during sleep. Unfor- 
tunately we cannot discuss tremor, because, in our opinion, 
absolutely nothing is known as to its real cause, 48 and because 
it is not our purpose to enter into clinical or diagnostic details. 

(b) Choreiform Movements. — According to Bonhoeffer, 
the choreiform movements that sometimes develop after a 
hemiplegia are usually caused by lesions of the superior cere- 
bellar peduncles, 49 which lesions would interrupt the centri- 
petal impulses that pass through the cerebellum on their way 
to the motor region of the cerebral cortex. The muscle tonus 
in these conditions is usually diminished, 50 which fact lends 

" See Mobius, Diagnostik, second edition ; Stcphan, Arch. f. Psych., 
vol. xviii. p. 734 ; vol. xix. p. 18. 

48 Monatshcfte f. Psych, u. Ncuro., vol. i. p. 6; vol. x. p. 383. 
"Bonhoeffer, Monatshefte I Psych, u. Ncur.. vol. iii. p. -'.V> 



472 CLINICAL PATHOLOGY 

some support to this hypothesis that the cerebellar function is 
affected. 

(c) Associated Movements. — In a variety of pathological 
conditions, certain voluntary movements are regularly accom- 
panied by other purposeless, so-called associated movements. 51 
As we have already stated, the innervation for a voluntary 
movement is extremely complex, impulses being sent to a great 
number of muscles. The muscular contractions that would 
result from all these motor impulses are, however, controlled 
by other impulses that come in from the periphery. If this 
peripheral control be lost, it is possible that certain acts should 
be accompanied by extra, purposeless movements which would 
be suppressed in the normal individual. The associated move- 
ments that may occur in tabes dorsalis are therefore related 
in a way to the ataxia, for both depend upon a loss of centri- 
petal, peripheral control. 

(d) Convulsions. — Convulsions may be of the clonic type, 
— i.e., the muscles are alternately contracted and relaxed with 
corresponding movements of different parts of the body; or 
they may be of the tonic type, — i.e., the contraction is continu- 
ous and the parts affected simply become rigid. Finally, the 
two forms of convulsions, tonic and clonic, may alternate with 
each other. 

Convulsions are undoubtedly caused by a stimulation of 
the motor tracts or nerve-cells. A disease of the cervical or 
dorsal cord may cause convulsive movements in the legs from 
an irritation of the motor tracts; lesions of the internal cap- 
sule or of the cerebral cortex may cause convulsions in the 
corresponding extremities, etc. It would appear, however, 
that the stimulation of the cerebral cortex is more liable to pro- 
duce convulsions than is stimulation of other parts of the 
motor apparatus. 

81 See Foerster, Die Mitbewegungen, Jena, 1903. 



THE NERVOUS SYSTEM 473 

Many poisons produce convulsions, some of which, such 
as the uraemic poison, are formed within the body during path- 
ological processes. It is impossible to say, however, upon 
which part of the central nervous system these poisons act. 

Epilepsy is apparently due to an excessive irritability of the 
central nervous structures. The convulsions themselves may 
be precipitated by sensory impulses from some part of the sur- 
face of the body, but more frequently they come on sponta- 
neously, or, at least, without any discoverable cause. The 
attack is often preceded by certain characteristic psychic or 
bodily warnings (aura). The patient then becomes uncon- 
scious and general convulsions occur, which are at first tonic 
but later clonic in character. 52 It is possible to induce tonic 
as well as clonic convulsions in animals experimentally by 
stimulating various parts of the brain, such as the medulla, 
the pons, and the sensory and motor regions of the cortex. Of 
these convulsions, none present so great a similarity to the at- 
tacks of epilepsy as do those that follow stimulation of the cere- 
bral cortex. The latter may be either fully developed or rudi- 
mentary in type, and they often continue after the stimulation 
has ceased. The similarity that exists between the convulsions 
of epilepsy and those that follow stimulation of the cerebral 
cortex favor the view that epilepsy is of cortical origin. This 
view is supported, furthermore, by certain clinical facts, such 
as the frequency of rudimentary epileptic attacks, the associated 
unconsciousness, the spread of the convulsions in accordance 
with the cortical representation of muscles, and the frequent 
occurrence of sensory aura. 

Disturbances of Sensation. — The pathology of sensation is 
so intimately associated with the mind itself that our consid- 
eration of this subject will necessarily be limited, for, as we 
have already said, we do not propose to discuss psychic 

■ Sec v. Biswangcr, in Nothnagcl System. 



474 CLINICAL PATHOLOGY 

changes. It will be necessary to limit our discussion in still 
another way, — viz., by omitting the special senses of sight and 
hearing, for these subjects require so much special knowledge 
that we cannot do justice to them. 

Disturbances of sensation may be either irritative or par- 
alytic in character, and the sensory mechanism may be injured 
at any point from its beginning in an end organ at the pe- 
riphery to its termination in the central perceptive part of the 
cerebrum. If the peripheral sense organ is injured, if conduc- 
tion of the impulse through the nerve or cord be interrupted, 
or if, finally, the connections in the brain be thrown out of 
function, then the sensation will be either distorted in some 
manner or it will not be perceived at all. 

In certain spinal or peripheral diseases the sensations are, 
indeed, perceived, but they travel at a slower rate of speed than 
normal. This occurs most frequently in tabes dorsalis and it 
most frequently affects the cutaneous sensation of pain. We 
do not know exactly how this delayed sensation is caused. 

When a certain injurious agent affects at one time a num- 
ber of nerve-fibres of different functions, then the sensory 
fibres usually resist the injury better than the motor fibres do. 
Under such circumstances, the motor fibres may be paralyzed, 
while the sensory fibres are merely irritated and cause pain. 
This combination of symptoms is seen especially from press- 
ure upon the spinal cord, in which case we have the character- 
istic picture of paraplegia dolorosa. 

Our whole knowledge of the external world comes to us 
through centripetal nervous impulses, all the functions of our 
bodies being more or less affected by them. Thus, the sensa- 
tions of light, sound, and temperature influence metabolism, 
muscular activity, and respiration. When one form of sensa- 
tion is lost, the others become more acute because more atten- 
tion is directed to them, the best known example of this being 
the acute sense of touch that is developed in blind individuals. 



THE NERVOUS SYSTEM 475 

The Cutaneous Sensations. — The nerves of pressure, pain, 
heat, and cold, each possess definite and characteristic ending's 
in the skin. 53 These delicately constructed end organs are 
almost certainly injured in some skin diseases, although, so 
far as I know, no thorough study of such injuries has yet been 
made. Diseases of the nerves or of the central apparatus may 
also affect the cutaneous sensations, and any one of the latter 
may be disturbed without the others being affected. Such 
" partial anaesthesias" may result from disease either of the 
nerves or of the central nervous system, but they are espe- 
cially frequent in tabes and in syringomyelia. The occurrence 
of such partial anaesthesias is of great practical and theoretical 
interest, for it implies that special nerves exist for each of the 
cutaneous sensations. In particular, it tends to prove that 
pain is due to the stimulation of special pain fibres, and not to 
the overstimulation of other varieties of fibres. The physio- 
logical observation that certain points in the skin are sensitive 
to pain alone and others to pressure alone, likewise supports 
this view. We may mention, however, that even so experi- 
enced an investigator as Goldscheider denies the existence of 
special nerves for pain. 54 

Lesions of the peripheral nerves may affect the different 
skin sensations to different degrees, and in this manner give 
rise to partial anaesthesias ; but the most pronounced instances 
of this condition are usually observed in diseases of the spinal 
cord. The fibres that transmit the various forms of cutaneous 
sensation apparently run in different parts of the cord, and, 
consequently, a limited lesion may block some of them and 
leave others intact. 

The path pursued by the sensory fibres in the central ner- 
vous system is an extremely complex one. A portion of the 

" See v. Frey, Bcrichtc d. Kgl. S. Gcs. d. Wissenssch., math-phys. Kl., 
March, 1895. 

"Goldscheider, Uchcr den Schmertz, Berlin, 1894. 



476 CLINICAL PATHOLOGY 

fibres that carry impulses to the brain certainly cross by way of 
the anterior commissure to the opposite side of the cord shortly 
after they enter it. This is the explanation of the Brown- 
Sequard symptom-complex. If one-half of the spinal cord be 
destroyed, the muscles on that side below the level of the lesion 
will be paralyzed, with an associated loss of the sense of posi- 
tion. The cutaneous sensations, that are interrupted, however, 
are those that come from the opposite side of the body below 
the lesion. 

When the sensory tracts reach the brain, they connect with 
various reflex and automatic centres, and some finally termi- 
nate in the cerebral cortex, apparently in the neighborhood of 
the motor areas that govern the movements of corresponding 
parts of the body. For this reason, lesions of the cortical motor 
area usually produce a diminution, though not a complete loss, 
of sensation in those parts of the body that correspond to the 
paralysis. So far as sight and hearing are concerned, we know 
that a sensation may be perceived without its meaning being 
recognized (soul blindness). For example, a patient may hear 
the ringing of a bell but yet be unable to tell what causes the 
sound. 

Every sensation produces at the same time a more or less 
definite impression of the place whence the sensation has come. 
In the case of the eyes and skin, this localization is very ac- 
curate, in the case of the mucous membranes near the outside 
of the body it is somewhat less accurate, and in the case of 
the deeper mucous membranes and the organs within the body, 
it is inaccurate and entirely unreliable. In certain nervous 
lesions, especially in those about the optic thalami, 55 the cu- 
taneous sensations are perceived but the ability to localize them 
is more or less lost. The exact nature of the changes that 
cause this loss of localization are not well understood. 

65 Horsley, Practitioner, 1904. 



THE NERVOUS SYSTEM 477 

The Orientation of our Bodies in Space. 56 — We derive in- 
formation as to the position of our bodies in space from a 
number of sources. Our eyes aid us by means of the images 
upon the retinae and by their motion within the orbits, the 
internal ear enables us to estimate changes in the rate or direc- 
tion of our movements, and other more or less valuable data 
are derived from the muscles, tendons, bones, joints, skin, etc. 
Even though we are not conscious of these various sensations, 
they all influence to some extent the conception that we have as 
to our position in space. 

Certain of these sensations may be lost without much effect 
upon our powers of orientation, for the reason that other sen- 
sations compensate for the lost ones. 57 The blind man moves 
about a room with great precision so long as he can use his 
sense of touch, and the deaf-mute hardly seems to be affected 
by the loss of his internal ears. It is an interesting fact, how- 
ever, that deaf-mutes do show a diminished power of orienta- 
tion, and that they behave quite differently from normal indi- 
viduals when they are turned about rapidly. 58 The tabetic 
who has lost certain of the sensory impulses coming from his 
legs depends very much upon his visual impressions, and if 
these be taken away from him by closing his eyes, he will often 
immediately fall to the ground. We see, therefore, that vari- 
ous disturbances of the peripheral sensory apparatus will dis- 
turb the sense of our position in space. The same effect may 
also result from lesions of the central mechanism in the brain ; 
above all, from lesions of the cerebellum. 

Dizziness. — We do not mean by dizziness a partial, transi- 
tory loss of consciousness, but a feeling that we are unable to 
control our equilibrium. This feeling usually results from an 
inability on the part of the central apparatus to harmonize the 

•'■" S'-<- Ilartmann, Die Oricntierung, Leipzig, 1902. 
" Sec P.ickcl, Deut. med. Wochens., 1901, No. 12. 
M Kreidl, Pfliiger's Arch., vol. li. p. 1 19. 



478 CLINICAL PATHOLOGY 

various centripetal impulses that come to it. 59 For example, 
if certain ocular muscles are paralyzed, then the images of an 
object looked at do not fall upon corresponding points of the 
two retinae as they normally should, and consequently the im- 
pressions derived from the two eyes will not correspond to each 
other. This causes a sensation of dizziness, which may usually 
be relieved if the impressions derived from the offending eye 
are excluded by closing it. Diseases of the semicircular canals, 
of the sacculus or utriculus, or of their central nervous con- 
nections in the cerebellum, will likewise cause dizziness, which 
dizziness is most marked when the disease is limited to one 
side only. 

In aural vertigo (Meniere's disease) the dizziness is usu- 
ally associated with disturbances of hearing. The cochlear 
branch of the auditory nerve transmits sensations of sound; 
whereas the vestibular branch, proceeding from the vestibule 
and the semicircular canals, carries impulses that are caused 
by changes in the rate or direction of our movements. The 
symptom of dizziness in aural vertigo undoubtedly results 
from disturbances in the impulses carried by the vestibular 
nerve. The associated anomalies of hearing are easily under- 
stood when we consider the close proximity of the two nerves 
and of their end organs. In many cases the sensations of dizzi- 
ness will disappear if the patient remain perfectly quiet; 
whereas in other cases they are constantly present even though 
the patient be still, and under such circumstances they are most 
harassing. 

The dizziness of aural vertigo is probably due to an irrita- 
tion of the vestibular nerve or of its connections rather than to 
a mere lack of function. The patient becomes dizzy because 
the impressions received from this source do not coincide with 
those received from other parts of the body. That the dizzi- 

59 See Hitzig, in the Nothnagel System. 



THE NERVOUS SYSTEM 479 

ness in these cases is not due to a mere lack of sensation from 
the internal ear is rendered probable by the fact that the typical 
symptoms of aural vertigo are rarely seen in those deaf-mutes 
in whom the internal ear is entirely functionless. 

Aural vertigo, as well as cerebellar vertigo, is frequently 
associated with other symptoms, such as vomiting, uncertainty 
in the voluntary muscular movements, especially in walking, 
and peculiar movements of the eyes. At present, however, it 
is impossible to explain these associated symptoms very satis- 
factorily. 

The sensation of dizziness may also be produced by many 
other causes, such as alcoholic intoxication, cerebral pressure, 
anaemia, and circulatory disturbances; yet the exact mode of 
its causation in these conditions is not known. 

Hyperalgesia. — Increased sensitiveness to painful stimuli 
that are applied to the skin has been observed in various dis- 
eases of the cord and of the more central endings of the sensory 
tracts. The transition from the normal to the pathological, 
however, is here a very gradual one, and individuals of a 
" sensitive" nature are certainly more susceptible to pain than 
are those of a phlegmatic type. The hypersensitiveness of hys- 
terical patients is probably of this perceptive character. Pe- 
ripheral abnormalities rarely give rise to hyperalgesia, although 
a neuritis will sometimes do so. 

Irritative Sensory Symptoms. — These differ from the pre- 
ceding in that the pain results not from hypersensitiveness to 
normal stimuli, but from a pathological irritation of the sensory 
mechanism. 

Itching is apparently caused in all cases by an irritation of 
the sensory organs in the skin, and it never results, so far as I 
am aware, from lesions of the conducting apparatus. It ac- 
companies most cutaneous diseases, but, for some unknown 
reason, it tends to be absent in certain lesions, such as those 
produced by syphilis. Not infrequently, itching is present 



480 CLINICAL PATHOLOGY 

when no cutaneous changes can be demonstrated, as, for exam- 
ple, in jaundice and diabetes. It is possible that in these cases 
the central apparatus is directly irritated. On the other hand, 
paresthesias, such as numbness and tickling, rarely accom- 
pany cutaneous diseases, but are caused usually by nerve or 
cord lesions. They have also been observed in the extremity 
that corresponded to a point of softening in the sensory sphere 
of the cerebral cortex. 60 They seem, therefore, to be caused 
by an irritation of the sensory tracts. 

Abnormal sensations of heat and cold are sometimes ex- 
perienced, but it is often difficult to distinguish these from the 
accompanying sense of pain. 

In our opinion, pain is normally caused by the stimulation 
of special pain fibres or sensory end organs. Heavy pressure, 
for example, will deform the skin and so stimulate the pain 
points. Pain also results from various inflammations and 
degenerations of the nerves, such as may be caused by alcohol, 
arsenic, malaria, etc. The nerves may also cause pain even 
when no demonstrable lesion is present, as happens in the 
neuralgias. 

It is remarkable that pathological processes within the cen- 
tral nervous system itself rarely produce much pain, so long as 
the peripheral nerves, the posterior roots, and the meninges re- 
main unaffected. Surgeons and physiologists have frequently 
demonstrated that the brain itself is practically insensible ; and 
although it cannot be denied that the pain fibres may be stimu- 
lated within the central nervous system, 61 yet the general fact 
remains that such a stimulation is not easily brought about. 

Many hysterical pains are probably of a central, " psychic" 
nature, but these are not related in any way to organic lesions 
of the cerebral cortex. 

60 Ziehen, Ergebnisse, etc., p. 604. 

61 Edinger, Ztft. f. Nervenheilk., vol. i. p. 262 ; Reichenberg, ibid., vol. 
xi. p. 349; Goldscheider, Ueber den Schmertz, Berlin, 1894, p. 24, etc. 



THE NERVOUS SYSTEM 481 

The Influence of the Nervous System upon the Tissue 
Nutrition. — The nutrition of a tissue depends primarily upon 
the activities of its individual cells. It is, indeed, necessary 
that food material should be supplied to it from the blood in 
sufficient quantities, yet this food supply alone does not stim- 
ulate the growth of the cell. That stimulus must come from 
the parenchyma itself. 

The exact part that the nervous system plays in this pro- 
cess is not at all clear. Beyond question, it exerts a very 
important influence upon the nutrition of certain tissues. Is 
this influence, however, due merely to the fact that the cells 
do not functionate properly without nervous impulses, or do 
the nerves contain some specific, nutritional, " trophic" fibres? 

The Effect of Separating a Nerve-Fibre from its Cell. — 
The nerve-fibres degenerate if they are separated from their 
ganglion cells, or if these cells are destroyed. This is explained, 
according to the neuron theory, on the assumption that the 
nerve-fibre, a long process of the ganglionic cell, dies when it 
is separated from its mother cell. Some, indeed, claim that 
the mere separation of the fibre from the cell, or, rather, the 
cessation of the influence that the cell exerts over the fibre, is 
not the cause of the degeneration, but that the latter is due 
directly to the traumatism of the operation. 62 It is possible, 
for example, experimentally to interrupt the transmission of 
nervous impulses through a fibre for a very long time without 
having any degeneration take place ; but although the ordinary 
nervous impulses were interrupted in such a case, we cannot 
be sure that the nutritional impulses were likewise affected. 

Even though the nerve-fibre is a part of the ganglion cell, 
the two must be, to a certain extent, independent of each other, 
for the fibres seem to be relatively much more susceptible to the 
action of certain toxins. The neuritis that follows the circula- 

" Bcthc, Allgem. Anat. u. Path. d. Ncrvensyst, Leipzig, 1903. 
31 



482 CLINICAL PATHOLOGY 

tion of these toxins in the blood apparently occurs either be- 
cause these fibres contain elements for which the toxins show a 
special affinity, or because the fibres are so remote from their 
nutritional centres, the cells. In many cases the nerves are ca- 
pable of exchanging material with their surroundings, as is 
evidenced especially by the fact that the tetanus toxin travels 
from the periphery to the cord through the axis cylinders. 
Possibly the toxins of other infectious diseases pursue this 
same course, and, if this were so, it might explain the special 
susceptibility of the nerve-fibres to the toxins of infectious 
processes. 

In some instances, as in a lead poisoning, different portions 
of the nerve-cell may be affected and consequently widely dif- 
ferent nervous symptoms may be produced. Certain of the sys- 
temic diseases of the spinal cord show various transitions into 
each other, and it is easy to conceive, for example, that the 
same cause might produce in one person a progressive muscular 
atrophy, in another, an amyotrophic lateral sclerosis, and in a 
third, a true spastic paraplegia, depending upon whether the 
pyramidal tracts or the motor cells of the anterior horns were 
more especially affected. 

When a ganglion cell is separated from its peripheral 
neuron, the former also undergoes certain changes, 63 which 
reach their height in about eighteen days. After this a portion 
of the injured cells may be restored to their normal condition. 
If the cell continue to be functionless, however, for the reason 
that the peripheral nerve cannot regenerate, then it gradually 
undergoes atrophy. This happens, for example, after amputa- 
tions, and the younger the individual the greater is the cell 
destruction. These facts are of considerable theoretical inter- 
est, for they show that the normal existence of a ganglion cell 
depends largely upon its ability to exercise its function. De- 

63 Marinesco, Neurol. Zrtbl., 1892, pp. 463, 505, 564; Nissl, Ztft. f. 
Psych., vol. xlviii. p. 197 ; Bethe, loc. cit. 



THE NERVOUS SYSTEM 483 

generation occurs because the sensory cells receive no impulses 
from the periphery and because the motor cells no longer re- 
ceive those indirect stimuli from the muscles and other tissues 
which normally play so great a part in the regulation of their 
activities. 

Nutritional Disturbances in the Muscles. — When the 
muscles are separated from the spinal cells that innervate them, 
they degenerate. The degenerative changes consist mainly in 
alterations of their chemical composition 64 and of their elec- 
trical irritability. In addition to these, a simple reduction of 
their contractile substance without degenerative changes takes 
place. 65 The reduction of the quantity of protoplasm is caused 
by the inactivity, and it is, therefore, an atrophy from disuse. 
The microscopical signs of degeneration, such as the granular 
and waxy degenerations, are not due to the separation of the 
muscles from the cord, but to some associated action of toxic 
substances. 

Changes in the Electrical Irritability of Muscles. 66 — After 
a muscle has been separated from its ganglion cells for a certain 
time, it responds abnormally to the electric current, and these 
changes constitute the so-called reaction of degeneration. It 
will no longer contract when its nerve is stimulated in any 
manner by the electric current, nor will it contract when it is 
itself directly stimulated by an ordinary interrupted current. 
Even the healthy muscle does not contract if very high fre- 
quency currents are applied to it, so that the loss of irritability, 
that the degenerated muscle shows toward an interrupted cur- 
rent, is merely one of degree. It is an exaggeration of the 
normal. In this respect, the degenerated muscle behaves like 

M Rumpf and Schum, Ztft. f. Nervenheilk., vol. xx. p. 445; Rumpf, 
Arcli. f. klin. Med., vol. lxxix. p. 158. 

" See Jamin, Exp. Untersuch. z. Lehre v. d. Atrophic gelahmter Mus- 
keln, Jena, 1904. 

•* See Erb, Electrotherapie, second edition; Stintzing, in Penzoldt- 
Stintzing's Handbuch d. spec. Therapic. 



484 CLINICAL PATHOLOGY 

a smooth muscle, for the latter also usually fails to respond to 
an interrupted current. 

The muscle that is separated from its ganglion cells will, 
however, respond for a long time to interruptions of the gal- 
vanic current, and it will, indeed, respond to a much weaker 
current than does the normal muscle. The contraction pro- 
duced by this current is not a prompt and short one, as is the 
case with the normal muscle, but it is very slow, and easily 
passes into tetanus. Such a slow contraction is also seen in 
the smooth muscle, in the fatigued striated muscle, and in myo- 
tonia congenita. Yet in all of these conditions the muscular 
contractions differ in other respects from that of the degen- 
erated striated muscle. 

The degenerated muscle, instead of responding more 
strongly to a closure of the current when the cathode is placed 
upon it, frequently contracts more strongly to the anodal clos- 
ure. It has been commonly assumed that this change is due to 
some fundamental alteration in its protoplasm, whereby it is 
rendered more irritable to the anodal closure; yet such does 
not seem to be the case. The muscle conducts the current, 
and, when the cathode is placed over its centre, for example, 
the current enters at the end and this receives an anodal stim- 
ulation. In the normal muscle the cathode causes a stronger 
contraction, because it is placed over the point of greatest 
irritability; i.e., the entrance of the nerve into the muscle. 
The centre of the degenerated muscle, however, early loses its 
irritability, and the extremities become the most irritable parts. 
When, therefore, an electric pole is placed over the centre of 
a degenerated muscle, and the current is closed, the end of the 
muscle receives the main stimulation. For this reason the 
maximal contraction is obtained when the anode is placed on 
the muscle, for the cathodal stimulus then acts upon the more 
irritable extremity of the muscle. 67 If the degenerated sar- 
67 See Wiener, Arch. f. klin. Med., vol. lx. p. 264. 



THE NERVOUS SYSTEM 485 

torius muscle of a frog be isolated and stimulated, it shows no 
diminution in its irritability to the cathodal closure as com- 
pared to the anodal closure. 68 

In certain instances, such as in trichinosis 69 and some 
muscular dystrophies, 70 the reaction of degeneration has been 
present without demonstrable lesions of the nerves. At the 
present time, however, these cases cannot be accepted as proof 
that the reaction of degeneration may occur independently of 
nervous lesions, for it is almost impossible to exclude changes 
in the finer nerve filaments. 

When a motor nerve is injured, but not entirely destroyed, 
then electrical changes of a less marked degree take place 
in the muscles, — the so-called partial reaction of degenera- 
tion. 71 

Atrophy from Cerebral Lesions. — When muscles are 
paralyzed from a cerebral lesion, the resulting atrophy de- 
velops more gradually and is of slighter extent than that which 
follows the division of a peripheral nerve, and it is, further- 
more, unaccompanied by any reaction of degeneration. In 
such cerebral paralyses only one form of stimulation, the vol- 
untary, is shut off from the paralyzed muscle. The reflex and 
automatic stimulations from the lower centres continue to act 
upon it. The paralyzed muscles frequently do contract from 
reflex stimulation, and even when they do not apparently do 
so, they still maintain their muscular tonus. The paralyzed 
muscle that retains a connection with its ganglion cells exhib- 
its a more active metabolism than the paralyzed muscle that is 
separated from these cells, 72 a further proof that the former 
maintains a certain amount of activity. 

'" Krchl, unpublished experiments. 

™ Nonne and Hoepfner, Ztft. f. klin. Med., vol. xv. p. 455. 

70 Schultze, Ucber d. mit Hypertrophic vcrbund. Muskelsehwund, Wies- 
baden, 1886. 

71 Stintzing, Arch. f. klin. Med., vol. xli. p. .41. 
"Zuntz, Bcrl. klin. Wochcns., 1878, No. 10. 



486 CLINICAL PATHOLOGY 

In certain instances, especially in the young, cortical 
lesions have been followed by marked changes in the lower 
neurons and rapid atrophy of the muscles. 73 The electrical 
reaction in these cases is usually qualitatively normal, although 
in a few the slow contraction of degeneration has been pres- 
ent. The upper neurons apparently exercise some influence 
upon the peripheral neurons, and when this is cut off in early 
life, the latter may degenerate. 74 

Muscular Atrophy from Diseases of the Joints. 75 — These 
atrophies about diseased joints often develop more rapidly and 
are more severe than those which are caused by cerebral 
lesions. As a rule, they do not affect equally all muscles about 
the joint, but they tend especially to injure the extensors. The 
severity of the muscular atrophy bears no definite relation to 
the intensity or variety of the joint lesion. The electrical irri- 
tability of the muscle is usually reduced, but no typical reac- 
tion of degeneration is present. This form of atrophy differs, 
therefore, from that caused by cerebral lesions in its intensity 
and the rapidity with which it develops, and from that caused 
by nerve-lesions in the absence of a reaction of degeneration. 

Various attempts have been made to explain the causation 
of these muscular atrophies about diseased joints. The French, 
following Charcot's lead, have generally considered that the 
nervous impulses sent from the joint to the cord influence the 
motor cells there, and that a disturbance of the impulses from 
these cells causes the atrophy. The Germans, following 
Strumpell, have been more inclined to attribute these muscular 
atrophies to an extension of the disease by contiguity from the 
joint to the muscle, though it must be admitted that, experi- 

73 Quincke, Arch. f. klin. Med., vol. xlii. p. 492 ; Steinert, Ztft. f. Ner- 
venheilk., vol. xxiv. p. 1. 

74 Goldscheider, Berl. klin. Wochens., 1894, p. 421 ; Steinert, loc. cit. 

75 See Charcot's Lectures; Charcot, Progres med., April 1, 1893; 
Strumpell, Munch, med. Wochens., 1888, No. 13. 



THE NERVOUS SYSTEM 487 

mentally at least, no inflammation of the muscle is necessarily 
present, 76 and that the muscles atrophy throughout their entire 
length, and not merely in the neighborhood of the joint. 
Finally, attention has been called to the fact that the most 
seriously affected muscles are precisely those whose movements 
are most limited by the joint disease, so that the atrophy is 
probably caused in part, at least, by disuse. 77 

The Muscular Dystrophies. — This disease, which tends to 
occur in families, is characterized by a very gradual atrophy 
of certain muscles. It usually begins in childhood or early 
youth. Several types have been described, but it seems very 
probable that they are all but different variations of the same 
disease. Anatomically, we find many atrophied fibres, and, in 
addition to these, there are usually a number of thickened 
fibres, which latter may, indeed, be so numerous that the 
muscle as a whole appears to be hypertrophied. The adipose 
tissue between the muscle-fibres is sometimes so increased in 
amount as to produce a large, weak muscle, the so-called 
pseudohypertrophy. In the great majority of these cases no 
reaction of degeneration is present, and in the few instances 
in which it has been found it is extremely difficult to exclude 
some slight involvement of the finer nerve-filaments. Even 
the presence of changes in the spinal cord, such as have been 
described, 78 do not permit us to assume that this disease is of 
central origin; for, as we have seen, an atrophy of the gan- 
glion cells may follow a primary peripheral condition, such as 
an amputation. In a few cases, classified among the dystro- 
phies, some complication may have caused the cord lesion. 

Nutritional Disturbances of Nervous Origin in the Bones 
and Joints. — After an acute anterior poliomyelitis in cliil- 

"Dtiplay and Cazin, Arch, gen., 1891, vol. i. p. 5. 

n Sulzer, Anat. Untcrs. ii. Muskelatro. artik. Ursprungs. Festschr. f. 
Hagenbach-Burckhardt, Basel, 1897. 

" Erb, Ztft. f. Nervenh., vol. i. pp. 13, 173- 



488 CLINICAL PATHOLOGY 

dren, the bones of the paralyzed extremities frequently fail 
to develop to their normal size; whereas, after the cerebral 
infantile palsies, their growth is rarely much affected. In the 
former cases, the absence of the varying pressures and move- 
ments, to which the bones are normally subjected, may diminish 
their blood-supply and so retard their development; but it is 
possible, on the other hand, that this retardation is due to an 
absence of specific, trophic influences. In adults, nutritional 
changes in the bones rarely result from diseases of the periph- 
eral motor neurons alone. 

In a variety of other nervous diseases, especially in syringo- 
myelia and tabes, as well as in certain peripheral lesions, very 
remarkable nutritional disturbances take place in the bones and 
joints. 79 The anatomical changes in the joints often resemble 
those of arthritis deformans, but they differ from these in cer- 
tain particulars, especially in the more abundant effusion, the 
greater destruction of the joint, the rapid course, and the fre- 
quent absence of all pain. In a certain proportion of these 
cases, the lesions are undoubtedly due to an absence of the 
senses of temperature and pain. I have myself seen a man 
with syringomyelia who frequently injured himself while at 
work from grasping live coals, who paid no attention to his 
wounds on account of the absence of pain, and who eventually 
developed the most pronounced deformities in his bones and 
joints. Such observations are not infrequent. 80 In locomotor 
ataxia, also, injuries are frequently overlooked on account of 
the loss of sensation in the joints and muscles. In spite of these 
observations, however, the opinion of the authorities is now 
gradually turning toward that of Charcot, who held that the 
arthropathies are caused, in many instances at least, by a loss 
of trophic impulses from the cord. Patients have been ob- 

79 Charcot's Lectures ; Weizsacker, in Bruns Beitrage, vol. iii. p. 22 ; 
Kredel, Volkmann's Vortrage, No. 309. 

80 Karg, Langenbeck's Arch., vol. xli. p. 101. 



THE NERVOUS SYSTEM 489 

served in whom the most severe joint destructions have fol- 
lowed within a few days after nervous lesions, without any 
demonstrable mechanical injury. 81 

In some nervous diseases the bones are abnormally thin, 
and they fracture from very slight causes, or even, to all ap- 
pearances, spontaneously. Various cord changes have been 
found in such patients, 82 and in some cases a neuritis has been 
present. Although a number of other explanations have been 
offered for this abnormally brittle character of the bones, it 
seems probable that a lack of trophic influences is the cause in 
many cases. 

The Influence of Nervous Diseases upon the Skin — It is 
well known that those parts of the skin which are exposed to 
continued pressure tend in time to become reddened and swol- 
len, and eventually to die. Such ulcerations, of which bed-sores 
furnish the most familiar examples, may develop under a 
great variety of conditions, depending mainly upon the nutri- 
tion of the cells and constancy of the pressure applied. They 
are seen especially in patients with nervous, infectious, or 
metabolic diseases, who have lain for a long time in one posi- 
tion. In a certain proportion of the nervous cases, for these 
are the ones that especially interest us, the ulceration is favored 
by the cutaneous anaesthesia, and by the soiling of the skin 
with urine and faeces, owing to a paralysis of the bladder and 
rectum. As evidence of the importance of these factors, we 
may instance the brilliant results that follow the proper care 
of this class of patients. While we must admit, therefore, that 
the anaesthesia and dirt are important factors in the causation 
of these ulcerations, yet, in my opinion, they are not the only 
causes that are present, for at times the ulcers develop very 
rapidly even when there is no loss of sensation and no loss of 
bladder or rectal control. In this last class of cases, trophic 

81 Charcot's Lectures; Riedel, Deut. Gescllsch. f. Chir., 1883, p. 93. 
Oppenheim and Sicmcrling, Arch. f. Psych., vol. xviii. pp. 98, 487. 



490 CLINICAL PATHOLOGY 

disturbances certainly play an important role. To what ex- 
tent such trophic disturbances and to what extent the other 
factors enter into the causation of the ordinary bed-sores that 
develop during nervous diseases can only be determined by 
modern observations during- proper care of the patient. 

Herpes Zoster. — This remarkable eruption is associated 
with disturbances of the peripheral nerves, usually an inflam- 
mation of the sensory ganglion itself or of the nerve. 83 

The mere loss of a sensory nerve or ganglion does not 
cause nutritional disturbances in the skin or mucous mem- 
branes. This has been sufficiently proved by the results of ex- 
tirpation of the Gasserian ganglion for facial neuralgia. 84 
After such extirpations trophic disturbances of the skin over 
the face or of the mucous membrane of the nose or mouth 
do not occur. Even the cornea and conjunctivia remain in- 
tact if protected from direct injury. The keratitis observed 
in animals after excision of the trigeminus is due to the dry 
condition of the eye. 85 Since in man the eye may be kept 
moist by proper precautions, no keratitis necessarily results 
after the nerve is severed. 

83 Head, Albutt's System of Medicine. 

84 Krause, Die Neuralgie des Trigeminus, Leipzig, 1896. 

85 E. v. Hippel, Graefe's Arch., vol. xxxv. p. 217. 



INDEX 



¥¥ 



Absorption in exclusion of bile 
from the intestines, 271 ; in in- 
testinal diseases, 291 ; in pan- 
creatic diseases, 279. 

Acetanilide, action of, on red blood- 
corpuscles, 147. 

Achylia gastrica, 241. 

Acid intoxications : Origin of 
acids, 339, 340 ; action of, on res- 
piration, 228, 342; action of, on 
heart, nervous system, etc., 342. 

Acidosis, in diabetic coma, 342; ex- 
perimental, 228, 338; in hepatic 
diseases, 344. 

Acids, organic, origin of, in intes- 
tinal contents, 341 ; in interme- 
diary metabolism, 339; toxic 
action of, 228, 338, 342. 

Acton bodies, 340; their source, 
340, 341 ; their toxicity, 342. 

^Ethyliden-lactic acid, in diabetic 
urines, 340. 

Agglutination, 172. 

Albuminuria, causes of, 421, 422, 
425, 426, 427, 431 ; in haemoglo- 
binsemia and haemoglobinuria, 
145, 149; relation of, to cedema, 
119; to nephritis, 425; varieties 
of albumin, 423, 427, 431. 

Albumosuria, 432 ; in fever, 400. 

Alcoholism, as a cause of bradycar- 
dia, 86; of cardiac hypertrophy, 
54; of cardiac weakness, 62; of 
physiological albuminuria, 423. 

Aleukemic leukaemia, 160. 

Alexins, 143, 165, 166. 

Alkaptonuria, 345. 

Alloxuric bodies. See Purin 
bodies. 



Altitude, effects of high, on blood, 
178-181 ; on respiration, 217. 

Amboceptors, 144, 166. 

Amido-acids in the urine, 336, 337. 

Ammonia, excretion of, as urea, 
337, 344 5 formation of, in body, 
337; function of, to neutralize 
acids, 337, 338; relation of, to 
hepatic disease, 344. 

Amyloid degeneration of the kid- 
neys, absence of heart changes 
in, 50; cedema in, 119. 

Anaemia, effect of, on heart, 66; on 
respiration, 221. 

Anaesthesia, partial, 475. 

Aneurysm of the aorta and hyper- 
trophy of the heart, 47. 

Angina pectoris, 105-107. 

Antitoxins, 167-171. 

Anuria, in haemoglobinuria, 149; in 
uraemia, 434, 436. 

Aortic insufficiency, 34; compen- 
sation, 36-38, 58 ; heart murmurs, 
100; pains in, 105; pulse in, 59; 
pulse-pressure in, no. 

Aortic stenosis, 38; bradycardia in, 
85 ; heart murmurs in, 101 ; 
hypertrophy of left ventricle in, 
39; pain in cardiac region, 105. 

Aortic tones, accentuation of, 96. 

Apoplexy, blood-pressure in, 450. 

Appetite, 262. 

Arrhythmia of the heart, 87 ; 
causes of, 93 ; extrasystoles in, 
88; true arrhythmias in, 91. 

Arsenurretted hydrogen, effect of, 
on bile, 265. 

Arterial paralysis, 112; symptoms 
of, 113; heart action in, 80. 
491 



492 



INDEX 



Arteries, movements of, 114; sig- 
nificance of, for the circulation, 
108; spasm of, in; tonus of, 
108. 

Arteriosclerosis, as a cause of car- 
diac hypertrophy, 46; of cardiac 
insufficiency, 62, 65; hemorrhage 
from, 59 ; heart sounds in, 97 ; in 
nephritis, 52; pulse-pressure in, 
no. 

Ascites, in anasarca, 116; in chylous 
and chyliform, 121. 

Asphyxia, 225 ; arterial spasm in, 
hi, 225; heart-rate in, 225; path- 
ogenesis of, 225 ; symptoms of, 
225 ; urine in, 417. 

Asthenic bulbar paralysis, 455. 

Asthma, bronchial, 206, 207. 

Asthma, cardiac, 104. 

Ataxia, 457-460. 

Atelectasis of the lungs, 215. 

" Athlete's heart," 53. 

Atmospheric pressure, effect of, on 
blood, 178; on respiration, 217. 

Atony of the stomach, 257. 

Atrophy of the muscles. See Mus- 
cular atrophy. 

Atropin poisoning, effect of, on 
heart-rate, 79; on secretion into 
the mouth, 231. 

Aural vertigo, 478. 

Autolysis, 335. 

Bacterial processes, in the bile-pas- 
sages, 268-270; in the intestines, 
284 ; in absence of bile, 272, 273 ; 
on varying food, 285 ; in the 
stomach, 249; in absence of acid, 
250; in presence of acid, 250; 
after introducing decomposable 
food, 252. 

Bactericidal action of blood serum, 
165, 189, 190. 

Basedow's disease. See Exophthal- 
mic goitre. 

Baths, cold, as a cause of albu- 
minuria, 422. 



Beer, effect of, on alimentary gly- 
cosuria, 349; on heart, 54; on 
stomach, 255. 

Belching, 260. 

Beta-oxybutyric acid in the urine, 
340; during diabetes, 342. 

Bile, action of, on pancreas, 282; 
effect of exclusion from the in- 
testines, 271 ; variations in 
amount and composition of, 265. 

Bile, stasis of, anatomical changes 
in the liver, 275 ; in cerebral 
symptoms, 276 ; in heart symp- 
toms, 84; lack of, in intestines, 
271. 

Biliary colic. See Gall-stones. 

Blood, in acid intoxications, 228; 
in anaemia, 128, 130, 136, 137; in 
low atmospheric pressures, 178; 
in carbonmonoxide poisoning, 
181, 220; in chlorosis, 131; in 
circulatory disturbances, 176, 177; 
in gout, 372; in hydraemia, 174; 
in leukaemia, 155 ; in phosphorus 
poisoning, 181, 229; in pseudo- 
leukaemia, 155; effect of, on res- 
piration, external, 221 ; internal, 
226, 228; effect of, on urine, 414, 
417, 429. 

Blood coagulation, after destruc- 
tion of red blood-corpuscles, 148; 
relation of, to quantity of fibrin, 
162. 

Blood-corpuscles, red, in anaemias, 
128 ; effect of low atmospheric 
pressure on, 178; of burns, 147; 
in chlorosis, 131 ; conversion of 
haemoglobin into methaemoglobin, 
142, 147; after hemorrhage, 126; 
regeneration of, 129; water con- 
tents of, 141. 

Blood-corpuscles, white, origin of 
various forms of, 150; leucocy- 
tosis, physiological, 150, and path- 
ological, 152; leucopenia, 154; 
variations of, in anaemias, 127, 
I3i } 136; in leukaemias, 155. 



INDEX 



493 



Blood-flow through the kidneys, 
effect of, on secretion of urine, 
414, 417; on albuminuria, 426. 

Blood plasma, distinction of, from 
serum, 162 ; amount of fibrin in, 
162. 

Blood-pressure, arterial, 109; dur- 
ing exercise, 29; effect of, on 
heart's action, 80, 83 ; increased, 
111; lessened, 112; physiologi- 
cal variations of, hi; in renal 
disease, 50; effect of, on secre- 
tion of urine, 415, 417. 

Blood-pressure, venous, increased, 
and its results, 76, 77, 116. 

Blood, quantity of, in body, diminu- 
tion of, 183; increase of, without 
change in serum, 181 ; with 
watery serum, 119, 174. 

Blood serum, in chlorosis, 131 ; 
contents of fat in, 163 ; proteids 
in, 164; salt in, 174; water in, 174; 
ferments in, 165 ; in pernicious 
anaemia, 137 ; toxic action of, 143. 

Blood supply to brain, 443 ; to, 
heart, 65 ; to kidneys, 414, 417, 
426. 

Bone lesions in nervous diseases, 
487. 

Bone marrow, in anaemia, 130, 140; 
in Hodgkin's disease, 159; in 
leukaemia, 157, 159. 

Botulism, 283. 

Bradycardia, in Adams-Stokes dis 
ease, 87 ; causes of, 83 ; signifi 
cance of, for the circulation, 87 

Bronchial stenosis, 205. 

Bronchiolitis exudativa, relation of, 
to asthma, 206. 

Bronchitis, interchange of gases in 
224 ; respiratory movements in 
205. 

Brown-Sequard paralysis, cause of 
476. 

Bulbar paralysis, salivation in, 233 

Burns, blood changes after, 147 
148. 



Calculi, biliary, 266; urinary, 438. 

Caloric needs of the body, 313, 314. 

Carbon dioxide, anaesthetic action 
of, 225 ; amount of, in the blood 
in acid intoxications, 228. 

Carbon monoxide poisoning, blood 
in, 220; respiration in, 221. 

Carcinoma of the stomach, diges- 
tion of proteids in, 248 ; secre- 
tion of hydrochloric acid in, 247. 

Carcinomatosis, anaemia in, 134, 138; 
proteid destruction in, 331. 

Cardiac impulse, 95 ; pain, 105. 
See Heart. 

Cardiograms, 95, 96. 

Castration, relation of, to obesity, 
329- 

Casts in urine, 429. 

Cell function, effect of, on tissue 
growth, 21 ; effect of nervous 
system upon, 481. 

Cerebral cortex, circulatory dis- 
turbances in, 443. 

Cerebral pressure, blood-pressure 
in, 450; choked disk in, 448; in 
chronic hydrocephalus, 447 ; in 
meningitis, 447; pulse in, 84, 
449; respiratory movements in, 
450; in brain tumors, 447. 

Cerebral symptoms, in anaemia, 
444; in Cheynes-Stokes respira- 
tion, 211; in hepatic toxaemias, 
277. 

Cerebral tumors, cerebral pressure 
in, 447- 

Cervical cord injuries, effect of, on 
temperature, 404. 

Charcot-Leyden crystals, in asth- 
matic sputum, 206, 208 ; in leu- 
kemic blood, 157. 

Cheynes-Stokes respiration, ail, 
450. 

Chlorosis, 130. 

Choked disk, 448. 

Cholera, Asiatic, faeces in, 293 ; in- 
creased susceptibility to, 287. 

Choreiform movements, 471. 



494 



INDEX 



Chylous and chyliform ascites, 121. 

Cilia, movements of, as a protec- 
tion to respiratory apparatus, 197. 

Circulation, in aortic insufficiency, 
35 ; in the arteries, 108 ; effect of 
arteries on, 108; in bradycardia, 
87; demands of, on normal, 25; 
relation of, between blood-press- 
ure and rate of flow, 24; effect 
of, on respiration, 223, 226; in 
tachycardia, 83 ; effect of, on 
urine, 414, 417; in the veins, 115; 
in cardiac weakness, 71-74. 

Circulatory disturbances, in the ar- 
teries, 108; in asphyxia, ill, 225; 
in the brain, 443 ; hydrasmia in, 
176; in infectious diseases, 113; 
in paroxysmal haemoglobinuria, 
146 ; effect of, on respiration, 223, 
226; in shock, 114; effect of, on 
urine, 414, 417; in the veins, 115. 

Coagulation of the blood. See 
Blood coagulation. 

Colic, biliary, 270; gastric, 263; 
intestinal, 310; urinary, 441. 

Colica mucosa, 296. 

Collapse in infectious diseases, cir- 
culatory changes in, 113; tem- 
perature in, 411. 

Coma, carcinomatous and enteroge- 
nous, 342; diabetic, 342, 343, 364. 

Compensation, cardiac, cause of 
break in hypertrophied hearts, 
63; in non-hypertrophied hearts, 
65 ; inefficiencies of the compen- 
sated circulation, 57. 

Compensatory regulations, in heart 
disease, 23 ; in chronic inanition, 
319, 382, 383; in respiratory dis- 
eases, 223. 

Complement. See Alexines. 

Concussion of the brain, 451. 

Congenital heart disease, lesions of, 
42; polycythemia in, 177. 

Constipation, 298-301. 

Contractures, 468. 

Convulsions, 472; epileptic, 473; 



in hepatic toxaemias, 277; in 
strychnine poisoning and tetanus, 
467; in uraemia, 433. 

Co-ordination, disturbances of, 456. 

Cord injuries as a cause of fever, 
404. 

Coronary sclerosis and embolism, 
sudden death in, 65. 

Coughing, advantages and disad- 
vantages of, 200; mechanics of, 
198. 

Creatinin in the urine of fever pa- 
tients, 390. 

Curschmanns' spirals in asthmatic 
sputum, 206. 

Cutaneous sensation, disturbances 
of, 475, 479- 

Cyanosis, congenital, 76, 177; idio- 
pathic, 178. 

Cystin calculi, 440. 

Cytolytic properties of the blood 
serum, 165. 

Decubital ulcerations, 489. 

Defecation, innervation of, 464. 

Degenerations, ot heart muscle, 67; 
of muscles, 483 ; of nerves, 481 ; 
of red blood-corpuscles in anae- 
mia, 128. 

Diabetes insipidus, 416, 429. 

Diabetes mellitus, acidosis in, 342, 
364; amount of urine in, 365; 
limits of assimilation in, 357; in 
coma, 342, 364; consumption of 
sugar in, 358 ; etiology of, 361 ; 
hyperglycaemia in, 352; mild and 
severe forms of, 352; nutritional 
disturbances in, 364; proteid de- 
struction in, 363 ; relation of, to 
liver, 357; to pancreas, 360, 362; 
renal diabetes in, 351 ; results of, 
362; thirst in, 365. 

Diacetic acid in the urine, 340. 

Diarrhcea, causes of, 295, 296; ef- 
fect of, on body, 298; faeces in, 
293- 

Diastole, variations in, 26, 70. 



INDEX 



495 



Digestive disturbances, from ab- 
sence of bile in intestines, 271 ; 
from gastric disease, 239; from 
bacterial decomposition, 249 ; 
motor, 252, 254, 293; psychic, 
264 ; secretory, 241 ; vomiting 
and belching in, 260; from intes- 
tinal disease, 282; bacterial, 284; 
meteorism in, 308; absorption in, 
291 ; stenosis in, 301 ; from dis- 
eases of the mouth and teeth, 
231 ; from diseases of the oesoph- 
agus, 236; from a lack of pan- 
creatic juice in the intestines, 
279; from an abnormal secretion 
of saliva, 232; from diseases of 
the throat, 235. 

Dilatation of the heart, 74; of the 
stomach, 256. 

Diphtheria toxin and antitoxin, 
167. 

Diuretics, action of, 415, 430. 

Diverticula of the oesophagus. See 
(Esophagus. 

Dizziness, 477. 

Dysentery, etiology of, 291. 

Dyspepsia, effect of, on the heart, 
84, 94 ; nervous, 264. 

Dysphagia, from oesophageal diver- 
ticula, 2^7, and stenoses, 236; 
from throat diseases, 235. 

Dyspnoea, asthmatic, 207 ; blood- 
pressure in, 48 ; cardiac, 103 ; as 
a cause of heart hypertrophy, 48; 
origin of, 229; subjective symp- 
toms in, 229. 

Dystrophies, muscular, 487. 

Eggs, albuminuria from, 422; toxic 

symptoms from, 291. 
Ehrlich's theory of immunity, 168. 
Emphysema of the lungs, 209; 

hearl hypertrophy in, 45, 210. 
Endarteritis obliterans, effect of, on 

extremities, 454. 
Endocarditis, 31, 32; in foetus, 42; 

effect of, on heart-rate, 94. 



Enzymes, of the blood, 165 ; in car- 
cinoma of the stomach, 248; in 
the gastric juice, 241 ; glycolytic, 
361. 

Eosinophilia, local and general, 154. 

Epilepsy, 473 ; urine during con- 
vulsions in, 417. 

Epithelium, of the kidneys, its per- 
meability to sugar and proteids, 
431 ; as a protection against 
micro-organisms, 285 ; of the re- 
spiratory tract and the value of 
cilia, 197. 

Ethereal sulphates in the urine as 
an index of putrefaction, 289. 

Exanthemata, immunity after, 190. 

Exchange of gases, in anaemia, 222 ; 
in bronchitis, 224; compensatory 
mechanisms in disturbances of 
external respiration, 223; in pul- 
monic and pleural diseases, 224. 

Excitement, influence of, on albu- 
minuria, 423 ; on heart action, 80, 
94; on intestinal peristalsis, 295. 

Exertion, effect of, on albuminuria, 
422; on cardiac insufficiency, 53, 
69; on heart-rate, 79; on size of 
heart, 29, 30. 

Exophthalmic goitre, cause of, 334; 
glycosuria in, 349; heart hyper- 
trophy in, 48; pulse-rate in, 80; 
pathological consumption of pro- 
teids and fats in, 332; relation 
of, to changes in thyroid gland, 
334- 

Expiration in stenosis of the air- 
passages, 204. 

Extrasy stoles, 88; causes of, 90, 91. 

Facial paralysis, effect of, on chew- 
ing, 231. 

Faecal stones as a cause of intes- 
tinal obstruction, 302. 

Faeces, bacterial contents of, 273, 
284, 301 ; after exclusion of the 
bile from the intestines, 271 ; in 
pancreatic disease, 279; stagna- 



496 



INDEX 



tion of, 298, 301 ; water contents 
of, increased, 292, 293; dimin- 
ished, 298. 

Fat storage in the body, 323, 324, 
325. See Obesity. 

Fat necroses, 281. 

Fatty exudates, 121 ; heart, 68. 

Fermentation, in the intestines, 288 ; 
in the stomach, 249, 250, 252; re- 
lation of, to gastric atony, 258. 

Ferments. See Enzymes. 

Fever, acidosis in, 390; effect of 
age and nutrition on, 405 ; in 
pernicious anaemia, 137; causes 
of, 399; diurnal variations in, 
376; effects of food on, 386, 397; 
glycogen in, 394, 403 ; heat losses 
in, 388; heat production in, 382; 
heat regulation in, 395 ; hysteri- 
cal, 402; in leuksemia, 158; me- 
tabolism in, 388, 391 ; in nervous 
diseases, 401 ; proteid destruction 
in, 388; pulse-rate in, 79; reflex, 
404 ; effect of, on respiration, 
205 ; significance of, for the body, 
408; symptoms of, 405. 

Fibrin, amount of, in the blood, 
162. 

Foreign bodies in respiratory pas- 
sages, removal of, 197-200. 

Fragmentation of the heart muscle, 
68. 

Gall-stones, colic in, 270; constitu- 
ents of, 266; dangers of, 270; 
formation of, 267; intestinal ob- 
struction from, 302; numbers of, 
266. 

Ganglion cells, relation of, to nu- 
trition of nerve fibres, 481. 

Gangrene, in diabetes, 364; in in- 
termittent claudication, 455 ; in 
nervous diseases, 489. 

Gastric diseases. See Stomach. 

Gastric juice, action of acid on in- 
testines, 253 ; acidity of, 240, 242; 
diminished, 247 ; increased, 242 ; 



absence of free acid in, 247; an- 
tiseptic action of, 249; hyper- 
secretion of, 243. 

Gastro-intestinal infections, 187, 
284-291. 

Gingivitis in scurvy, 232. 

Glomeruli, sensitiveness of epithe- 
lium, 425. 

Glottis, spasm of the, 202. 

Glycogen, in diabetes, 357; in 
fever, 394, 403. 

Glycosuria, alimentary, 348; from 
beer, 349; causes of alimentary, 
349; experimental, 349, 351, 360; 
from injuries, 352; effect of kind 
of sugar upon, 353; phloridzin, 
349; renal, 351. 

Goitre, effect of, on heart, 80; on 
respiration, 201. 

Gonorrhceal infections, 31. 

Gout, attacks of, 371 ; deposits in, 
370, 374 ; theory of, 375 ; uric acid 
in blood in, 2>72\ in urine, 373. 

Granular kidney, hemorrhages in, 
59; heart- and blood-pressure in, 
49; relation of, to arteriosclero- 
sis, 52; urine in, 415, 420. 

Graves's disease. See Exophthal- 
mic goitre. 

Haemoglobin, in changes of atmos- 
pheric pressure, 180; in chloro- 
sis, 131 ; conversion of, into 
methsemoglobin, 142, 147 ; rela- 
tion of, to respiration, 221 ; solu- 
tion of, in blood, 141, 146. 

Haemoglobinaemia, 141, 143. 

Hemoglobinuria, paroxysmal, 145. 

Headaches, in cerebral ansemia, 
445- 

Heart (see Cardiac), adaptabil- 
ity of the, 23 ; accommodative 
power of normal, 25, and of hy- 
pertrophied muscle, 58; capabili- 
ties of hypertrophied, 28, 58; 
elasticity and contractility of, 26; 
fatigue of, 69; effect of nervous 



INDEX 



497 



system upon, 27; relation of 
weight of, to body weight, 29; 
reserve strength of, 58; varia- 
tions in the amount of blood ex- 
pelled by, 28. 

Heart dilatation, compensatory, 35, 
41, 57. 74; non-compensatory, 75; 
in paroxysmal tachycardia, 81. 

Heart hypertrophy, 28; ability of 
heart to hypertrophy, 55 ; causes 
of, in general, 28; compensatory, 
57; concentric and eccentric, 56; 
definition of, 29 ; insufficiency of, 
61, 63; effect of, on lungs and 
respiration, 58 ; of both ventri- 
cles, in pericarditis, 48 ; in renal 
disease, 49; of left ventricle, in 
aortic aneurysm, 47 ; in aortic in- 
sufficiency, 34; in aortic stenosis, 
38; in arteriosclerosis, 46; in 
mitral disease, 40; in stenosis of 
the aorta, 47; of the right ven- 
tricle, in mitral disease, 39, 43 ; 
in pulmonary disease, 44. 

Heart, impulse of. See Cardiac 
impulse. 

Heart murmurs, 100-102. 

Heart muscle, relation of diseases 
to function, 65-68. 

Heart, palpitation of, 103. 

Heart poisons, accelerating, 79; 
causing irregularities, 94 ; slow- 
ing, 84. 

Heart sounds, 96-100. 

Heart spasm. See Angina pectoris. 

Heart, valvular disease of, 30; 
causes of, 30; combination of 
lesions of, 42, 43 ; congenital af- 
fections of the right side of, 42; 
extracardial effects of, 58-60. 

Heart, weakness of the, effect of, 
when both ventricles weaken, 71 ; 
when left ventricle weakens, jj ; 
when right ventricle weakens, 
73; weakness of hypcrtrophied 
hearts, 63 ; primary weakness, 
65 ; relation of, to angina pec- 



toris, 106; effect of, on secretion 
of urine, 417, 426. 

Heart, work of the, on exertion, 
29, 30 ; factors that determine, 23 ; 
relation to hypertrophy of, 28 ; in- 
creased work of left ventricle, 46 ; 
of right ventricle, 43; relations 
of, to subjective symptoms, 103. 

Heat, losses of, in the body, in 
fever, 384; production of, 382; 
normal regulation of, 2>77 '> regu- 
latory mechanism of, 395. 

Heat-stroke, 379. 

Hemiplegia, cerebellar, 452. 

Hemorrhages, in arteriosclerosis, 
59; as a cause of anaemia, 126, 
128; of hydrsemia, 174; of leu- 
cocytosis, 127 ; in leukaemia, 158. 

Hepatic toxaemia, 277. See Liver. 

Hernia, 302. 

Herpes zoster, 490. 

High altitudes, effect of, on blood, 
178; on respiration, 217. 

Hodgkin's disease, blood in, 155; 
fever in, 158; relation of, to 
tuberculosis, lymphosarcoma, and 
leukaemia, 155, 158. 

Homogentisic acid, 345. 

Hunger, cause of, 262. 

Hydraemia, 174 ; relation of, to 
cedema, 119; with water reten- 
tion, 174, 176; without water re- 
tention, 175. 

Hydrocephalus, chronic, 447. 

Hydrochloric acid, in gastric car- 
cinoma, 248 ; in gastric contents, 
240, 242; hyperacidity, 242, and 
its effects, 246; subacidity, 247. 

Hydrocyanic acid poisoning, effect 
of, on internal respiration, 229. 

Hydronephrosis, mechanism of pro- 
duction of, 419. 

I [yperalgesia, 479. 

Hyperglycemia, 352. 

Hysteria, ana-sthesia in, 460; diar- 
rhoea in, 395; fever in. 40a; heart 

action in, 80; metcorism in, 309. 



3- 



498 



INDEX 



Immune bodies, 144, 166. 

Immunity, acquired, 190; active, 
193; inherited, 189; passive, 194; 
specific, 190 ; theory of, 195. 

Inanition, as a cause of anaemia, 
134. 135; causes of, 316; as a 
cause of hydraemia, 174; organs 
mostly affected by, 318; partial, 
318; results of, 318; salt me- 
tabolism in, 318. 

Incoordination, 456. 

Indol, toxic effect from, 290. 

Infectious diseases, albuminuria in, 
427, 431; anaemia in, 134; col- 
lapse in, 113, 411; heart compli- 
cations in, 30, 34, 66; hydraemia 
in, 174; immunity after, 190; 
limitation of metabolism in long- 
continued, 319; proteid, destruc- 
tion in, 331; pulse in, 79, 86; 
saliva in, 232. 

Inflammatory oedema, 118. 

Inspiratory disturbances, in paraly- 
sis of the vocal cords, 204; in 
spasm of the vocal cords, 202; 
in stenosis of the larynx or tra- 
chea, 203. 

Insufficiency, of heart valves, aortic, 
34; hypertrophied hearts, 63; 
mitral, 40; tricuspid, 42; mus- 
cular, 33. 

Intermediary bodies, 144, 166. 

Intestinal disease, as a cause of 
anaemia, 134, 139; causes of 
bacteria in, 286; disturbances of 
motility in, 293 ; poisons in, 282 ; 
protozoa in, 291 ; secretory dis- 
turbances in, 293 ; effect on ab- 
sorption in, 291 ; pain in, 310. 

Intestinal gases, action of, on in- 
testinal movements, 309; origin 
of, in health, 308; in gastro- 
intestinal disease, 309; in steno- 
sis of the intestinal tract, 304. 

Intestinal movements, decreased 
peristalsis, 298-301 ; increased 
peristalsis, 295—298 ; normal, of 



colon, 294 ; of small intestines, 

293 ; in obstruction, antiperi- 

stalsis, 306 ; cessation of, 306. 
Intestinal obstruction, causes of, 

301-303 ; course of, 306 ; results 

of, 305. 
Intestinal parasites, as a cause of 

anaemia, 139 ; of eosinophilia, 154. 
Intestines, spasm of, as a cause of 

constipation, 301 ; in obstruction, 

305. 
Intussusception, mechanism of, 303. 
Iron, deposits of, in the liver owing 

to excessive destruction of red 

blood-corpuscles, 128. 
Iron, lack of, as a cause of anaemia, 

135- 
Islands of Langerhans in diabetes, 

362. 
Itching in diseases of the sensory 

cutaneous end-organs, 479. 

Jaundice, 273-277 ; in anaemia, 140 ; 
heart action in, 84, 277. 

Joint disease, as a cause of muscu- 
lar atrophy, 486; in nutritional 
disturbances, 488. 

Jugular pulse, in blocked heart, 87; 
in extrasystoles (see Figs. 3 and 
4) ; in paroxysmal tachycardia, 81. 

Kidneys, calculi in, 438; function 
of, as regulators of the composi- 
tion of the blood, 429-431 ; hyper- 
trophy of one, 418 ; relation of, 
to albuminuria, 420-426, 431 ; to 
glycosuria, 431 ; to haemoglobinae- 
mia, 149 ; to uraemia, 433 ; secre- 
tion of, with diminished circula- 
tion, 417, 426; with increased 
circulation, 414. 

Kidneys, inflammation of, albu- 
minuria in, 425 ; blood-pressure 
and heart hypertrophy in, 49; 
cardiac weakness in, 62; oedema 
in, 118; uraemic manifestations 
in, 433 ; urine in, 415, 425. 



INDEX 



499 



Lactosuria, 349. 

Laryngeal stenosis, effect of, on re- 
spiratory movements, 201-204. 

Lead poisoning, anaemia in, 134; 
arterial spasm in, 111 ; as a cause 
of gout, 372. 

Leucocytes. See Blood-corpuscles, 
white. 

Leucocytosis, after a hemorrhage, 
127; pathological, 152; physio- 
logical, 150, 151. 

Leukaemia, 155-162. 

Levulose, alimentary levulosuria, in 
hepatic disease, 349; in diabetes 
mellitus, 352. 

Lipaemia, 163. 

Lipase, action of bile on, 272 ; in 
gastric contents, 241 ; as a cause 
of fat necroses, 281. 

Liver, diseases of, acute yellow 
atrophy, 279, 340 ; amido-acids in, 
336, 22>7\ excretion of ammonia 
in, 344; formation of acids in, 
340, 344; effect on bile, 265, 273; 
on metabolism, 344 ; on urine, 
344- 

Liver, functions of, conversion of 
carbohydrates into fats, 360; gly- 
cogenic function, 348; in dia- 
betes, 357 ; in fever, 394, 403 ; 
upon poisons absorbed from in- 
testines, 289; urea formation, 
344- 

Lungs, antiseptic action of, 185 ; in 
chronic passive congestion, 59 ; 
distention of, in asthma, 206; in 
paroxysmal tachycardia, 82; loss 
of elasticity in, 209; infections of, 
186. See also Emphysema, etc. 

Lymph, composition of, 121 ; flow 
of, 1 16. 

Lymphatics, effect of an occlusion 
on, 117. 

Malaria, anaemia in, 134. 
Masturbation, effect of, on heart 
action, 94. 



Mediastinitis, heart hypertrophy 
in, 48; pulsus paradoxus in, 94. 

Megaloblasts, 136. 

Meniere's disease, 478. 

Meningitis, cerebral pressure in, 
447- 

Mercury, absorption of, through the 
skin, 184 ; ptyalism from, 233 ; 
stomatitis from, 232. 

Metabolism, ammonia formation in, 
227 ; in fever, 388-392 ; organic 
acid formation in, 339; proteid 
destruction in, 330; proteids, ab- 
normal products from, 335 ; purin 
bodies, formation and excretion 
of, in, 368; action of thyroid 
gland upon, 332, 334. 

Meteorism, 308-310. 

Micro-organisms, in bile, 267, 268, 
270; in intestinal diseases, 284; 
in mouth diseases, 231 ; in ne- 
phritis and albuminuria, 427, 432 ; 
obstruction to their penetration 
into the body, 184; in valvular 
diseases, 31. 

Micturition, nervous disturbances 
of, 463. 

Mitral insufficiency, 40; compensa- 
tion in, 40; distribution of blood 
in, 41; heart murmurs in, 100; 
heart sounds in, 97, 101. 

Mitral stenosis, 39; compensation 
in, 39; heart murmurs in, 101 ; 
heart sounds in, 97, 98. 

Monosodium urate in gout, 370, 374. 

Motility, disturbances of, from in- 
coordination, 456; from inter- 
mittent claudication, 454; from 
lesions of the motor tracts, 453 ; 
from muscular disease, 454 ; from 
psychic paralyses, 453; from dis- 
turbances of reflexes, 462. 

Mouth, affections of the, 231. 

Movements, effect of centripetal 
impulses Upon voluntary, 456; of 
exaggeration of reflexes, 462; in- 
testinal, 293. 



500 



INDEX 



Mucin in the urine, 421. 

Mucus in the air-passages, value of, 
198. 

Muscarin, action of, on the heart, 
66. 

Muscles, consumption of sugar in, 
361. 

Muscular atrophy, degenerative, 
483 ; reaction of degeneration in, 
483 ; from disuse, 483 ; the dys- 
trophies in, 487; in joint disease, 
486. 

Muscular insufficiency of the heart, 

33- 

Myasthenia gravis. See Asthenic 
bulbar paralysis. 

Myocarditis, in hypertrophied 
hearts, 60 ; primary, 66 ; in val- 
vular disease, 32, 33. 

Myotonia congenita, 455. 

Myxcedema, thyroid function in, 
334- 

Nephritis. See Kidneys, inflamma- 
tion of. 

Nerves, degeneration of, 481, 483. 

Nervous diseases, anaemia in, 134; 
constipation in, 299, 301 ; diar- 
rhoea in, 295 ; fever in, 401-405 ; 
from gastric dilatation, 259. 

Nervous system, in acidosis, 342 ; 
relation of, to diabetes, 351, 361, 
366; motor symptoms of, 452- 
462, 471-473 ; influence of, upon 
tissue nutrition, 481-489 ; reflexes 
of, 464-468; sensory disturb- 
ances of, 473-480; sympathetic 
centre for micturition of, 463. 

Neurasthenia, constipation in, 299, 
301; diarrhoea in, 295; heart ac- 
tion in, 80, 94. 

Neurin, toxic action of, 291. 

Nitrogenous equilibrium, 320. 

Nose, relation of its diseases to 
asthma, 207. 

Nourishment in relation to albu- 
minuria, 422. 



Nursing infant, effect of food upon 
intestinal flora of, 285; effect of 
nasal obstruction upon feeding, 
201. 

Nutrition, caloric needs of the body 
in, 312; necessary constituents of 
the food in, 312; proteid needs 
of the body in, 315; qualitative 
changes in, 335 ; quantitative 
changes in, 312; nitrogenous 
equilibrium in, 320; undernutri- 
tion in, 316. 

Nutritional disturbances, from de- 
struction of fats, 333 ; of pro- 
teids, 330; in diabetes mellitus, 
362; in fever, 388-392; effect of, 
on heart muscle, 66; from 
nervous lesions, 481-490; from 
obesity, 325 ; from the action of 
toxic substances, 332. 

Obesity, 326-329; relation of, to 
diabetes, 361. See also Fat 
storage in the body. 

CEdema, 1 16-124. 

(Esophagus, diverticula, 237; mus- 
cular spasm in, 238 ; pain in, 239 ; 
rupture of, 239; stenosis of, 236. 

Ophthalmoplegia as a cause of diz- 
ziness, 478. 

Optic neuritis, in cerebral pressure. 
See Choked disk. 

Orientation of the body in space, 
dizziness, 477-478. 

Oxalate calculi, 440. 

Oxidative processes in fever, 391. 

Oxy-acids, their origin in the inter- 
mediary metabolism, 339. 

Pain, in angina pectoris, 106 ; causes 
of, 480; delayed, 474; in gastric 
disorders, 263 ; in the heart re- 
gion, 105 ; in intestinal diseases, 
310; in mouth diseases, 232; in 
oesophageal diseases, 239; psy- 
chic, 480 ; in respiratory diseases, 
230 ; in urinary diseases, 441. 



INDEX 



501 



Palpitation of the heart, 102. 

Pancreas, action of bile upon, 282; 
effect of a lack of pancreatic se- 
cretion upon intestinal digestion, 
279; fat necroses, 281. 

Paralyses, 452-455 ; Brown-Se- 
quard, 476 ; psychic, 453 ; in urae- 
mia, 433- 

Paroxysmal tachycardia, 81. 

Pericardial adhesions as a cause of 
heart hypertrophy, 48 ; of the 
pulsus paradoxus, 94. 

Periosteal reflexes, 464-466; effect 
of an exaggeration upon move- 
ments, 462. 

Peritonitis, bradycardia in, 84; vas- 
cular changes in fatal cases of, 
"3- 

Pernicious anaemia, 136. 

Pertussis, nature of paroxysms in, 
202. 

Phagocytosis, theory of, 194. 

Phloridzin poisoning, 349, 350. 

Phosphatic calculi, 440. 

Phosphorus poisoning, acidosis in, 
339; bile in, 266; blood in, 181; 
internal respiration in, 229; 
jaundice in, 274; qualitative 
metabolic changes in, 337; urine 
in, 349- 

Pigmentation in anaemia, 140; in 
jaundice, 273. 

Plethora, 181, 182; hydraemic, 176. 

Pleuritic exudate, effect of, on res- 
piration, 213; on interchange of 
gases in the lungs, 224. 

Pleuritic obliteration as a cause of 
cardiac hypertrophy, 46. 

Pneumonia, autolysis of exudate 
in. 336; hypertrophy of right 
ventricle in, 45 ; interchange of 
gases in the lungs in, 224. 

Pneumothorax, 214; interchange of 
gases in the lungs in, 224. 

Poikelocytosis, in anaemia, 128, and 
in pernicious anaemia, [36. 

Poisoning, as a cause of albuminu- 



ria, 427; of anaemia, 134, 138, 
139 ; bile in, 265 ; blood changes 
in haemoglobinaemia, 142, 143 ; in 
leucopenia, 154; in methaemoglo- 
bin, 147 ; in polycythemia, 181 ; 
of intestinal origin, 282, 288-291 ; 
jaundice from, 274, 275; pro- 
teid decomposition in, 332; as a 
cause of respiratory disturbances, 
220, 228, 229. 

Polychromatophilia, 129. 

Polycythemia, 177-189. 

Polyuria, in diabetes insipidus, 416; 
in diabetes mellitus, 365; from 
drinking excessive quantities, 
429; in nephritis, 415; from 
paralysis of the renal nerves, 416. 

Portals of entry for infections, 184. 

Posture, effect of, on albuminuria, 
423- 

Potassium chlorate, action of, on 
red blood-corpuscles, 147, 148. 

Potassium salts in their relation to 
uraemia, 435. 

Precipitins, 171. 

Pregnancy, effect of, on the heart, 
55- 

Proprionic acid in the urine in 
metabolic diseases, 340. 

Proteid needs of the body, 315, 

319. 

Proteids, of blood serum, 163, 164; 
effect of, upon heat production, 
322 ; metabolism of, qualitative 
changes in, 335 ; quantitative 
changes in, 330 ; urinary, 427, 
428, 431. 

Proteids, pathological destruction 
of, in cachexias, 331 ; in dia- 
betes, 363 ; in exophthalmic 
goitre, 332; in fever, 388. 

Protozoa, as causes of anaemia, 134 ; 
of dysentery, 291 ; of fever, 399. 

I'sctidiK-roti]), 202. 

Pseudoleukemia. Sec Hodgkin's 
disease. 

Ptomaines, formation of, in intes- 



502 



INDEX 



tines, 290, 291 ; introduction of, 
into intestines, 283. 

Ptyalism, 233. 

Puerperium, bradycardia of, 87. 

Pulmonary circulation, 21 ; in com- 
pensated valvular lesions, 58; 
effects of disturbances upon the 
right ventricle, 43. 

Pulmonary diseases. See Lungs. 

Pulmonary stenosis, 42. 

Pulmonic second sound, accentua- 
tion of, 97 ; reduplication of, 98 ; 
in renal diseases, 51. 

Pulse, arterial, in aortic insuffi- 
ciency, 59; in bradycardia, 83- 
85 ; in Cheynes-Stokes disease, 
211; irregular, 87; in palpita- 
tion, 102; in tachycardia, 78; 
paroxysmal, 81. 

Pulse-pressure, 109. 

Pulse, venous, 77. 

Pulsus, alternans, 92; bigeminus, 
91 ; paradoxus, 94. 

Puncture of the brain, as a cause 
of fever, 394, 403; as a cause of 
glycosuria, 351. 

Pupils in Cheynes-Stokes phenom- 
enon, 211. 

Purin bodies, 368. 

Reaction of degeneration, 483. 

Reflexes, disturbances of deep and 
superficial, 464-467; effect of, on 
heart, 80, 84, 94; on micturition 
and defecation, 463 ; on saliva, 
233 ; on voluntary movements, 
462; in strychnine poisoning and 
tetanus, 467. 

Regeneration of red blood-cor- 
puscles, 128, 129. 

Relapsing fever in Hodgkin's dis- 
ease, 158. 

Renal diabetes, 351. 

Respiration, external, rapid, 205, 
216 ; slow, 203 ; deep, 203, and 
superficial, 205 ; Cheynes-Stokes 
phenomenon, 211; effect of ste- 



nosis of air-passages upon, 201 ; 
of changes in pulmonary mem- 
branes upon, 216; of the compo- 
sition of the blood upon, 221, 223; 
of the atmospheric pressure upon, 
217 ; of the composition of the 
air upon, 220 ; of fever upon, 205. 

Respiration, internal, 226-228. 

Respiratory apparatus, methods of 
removing foreign material from, 
197. 

Respiratory centre, sensitiveness to 
changes in the gases in the blood, 
211, 225. 

Respiratory disturbances, in anae- 
mia, 221, 223; in asthma, 206; 
in asphyxia, 225 ; in bronchitis, 
205 ; in diabetic coma, 342 ; in 
diminished respiratory surface, 
216; in emphysema, 209; in 
heart diseases, 58, 223 ; in im- 
purities in the inspired air, 217 ; 
effect of, on total interchange of 
gases, 224; on interchange of 
gases with the tissues, 226; in 
changes of irritability of the re- 
spiratory centre, 211; in paraly- 
sis of the respiratory muscles, 
208 ; from poisons in the inspired 
air, 220 ; in pleurisy and pneumo- 
thorax, 213, 224. 

Rheumatism, as a cause of heart 
disease, 31 ; as a cause of mus- 
cular atrophy, 486. 

Rhythm of the heart, normal and 
pathological, 77, 96. 

Right-sided heart disease, 41 ; cya- 
nosis in, 76, 177. 

Saliva, anomalies in secretion and 

composition of, 232—234. 
Sarcolactic acid in the urine, 339. 
Scurvy, mouth symptoms of, 232. 
Secretion, disturbances of, gastric, 

241 ; intestinal, 293 ; salivary, 232. 
Semicircular canals in relation to 

sense of dizziness, 447, 478. 



INDEX 



503 



Sensory disturbances, cutaneous, 
475; delayed sensation of, 474; 
from the heart, 105 ; from the 
intestines, 310; irritative sen- 
sory symptoms, 479; localization 
of sensations, 476; from the 
lungs, 230 ; effect of, on motility, 
459; painful sensations of, 479; 
sense of position of, 477; of the 
stomach, 262. 

Serum of the blood, agglutination, 
172; antitoxins, 167; cytolytic 
properties of, 165; fat in, 163; 
ferments in, 165 ; inactivation and 
reactivation of, 165 ; precipitins 
in, 171 ; proteids in, 163-164. 

Shock, surgical, 114. 

Side-chain theory, 167. 

Skee runners, hypertrophy of the 
heart in, 30. 

Skin, blood-vessels in fever of, 385, 
387; nutritional disturbances of, 
489; water excretion in fever of, 
386. 

Skin reflexes, 467. 

Smoking. See Tobacco. 

Sneezing, 198. 

Spasm of the glottis, 202. 

Spasm of the intestines, as a cause 
of colic, 310; of constipation, 
301 ; in obstruction, 305. 

Spasm of the pylorus, as a cause of 
gastric dilatation, 256, 257. 

Spleen, enlargement of, in hsemo- 
globinaemia, 141 ; in leukaemia, 
158, 159- 

Sputum in asthma, 206. 

Stasis, venous, 76, 77. 

Stenocardia. See Angina pectoris. 

Stenosis, of the cardiac orifices, 38, 
39, 42; of the intestines, 301 ; of 
the oesophagus, 236; of the py- 
lorus, 256; of the respiratory 
passages, 201. 

Stomach, affections of, as a cause 
of anaemia, 134, 138; as a cause 
of cardiac arrhythmia, 94. 



Stomach, atony of, 257. 

Stomach, dilatation of, absorption 
from, 258, 259; bacterial decom- 
positions in, 249; causes of, 256- 
258; motility of, 254; nervous 
symptoms of, 259. 

Stomach, movements of, 252-254. 

Stomach, secretion of. See Gastric 
juice. 

Stomatitis, 231. 

Strangulation of the intestines, 307. 

Strychnine poisoning, convulsions 
in, 467 ; urine in, 417. 

Subjective disturbances, cardiac, 
105 ; dyspeptic, 262 ; intestinal, 
310; respiratory, 229. 

Sugar in the blood, normally, 347 ; 
in diabetes, 352; in transitory 
glycosurias, 351; in phloridzin 
poisoning, 349; in renal diabetes, 
351- 

Surgical shock, 114. 

Swallowing, 235. 

Syncope, 444. 

Tachycardia, 78-83. 

Temperature of the body, influ- 
ence of the brain upon, 402, 403 ; 
in collapse, 411; diurnal varia- 
tions in, 376; in fever, 381; in 
heat-stroke, 379; pulse-rate in re- 
lation to, 79 ; regulation of, in 
health, 377; in fever, 381, 395; 
subnormal, 412. 

Tenesmus, rectal, 311; vesical, 441. 

Tetanus, causes of insusceptibility 
in, 169, 170; convulsions in, 467, 
468 ; formation of antibodies in, 
168, 169; spread of toxin in, 467. 

Tetany, relation of, to gastric dila- 
tation, 259. 

Thomsen's disease. Sec Myotonia 
congenita. 

Thmat affections, 235. 

Thyroid gland, 333; myxcedema, 
334; effect <>f, <>n metabolism, 334. 

Sec also Exophthalmic goitre. 



504 



INDEX 



Tobacco, as a cause of cardiac 
arrhythmia, 94; of bradycardia, 
86; of palpitation, 103. 

Toluylendiamin, action of, on se- 
cretion of bile, 266. 

Tonsils, as portals of entry for in- 
fections, 185. 

Tonus of the arteries, effect of, on 
blood-pressure, 108. 

Toxic albuminurias, 427. 

Toxic symptoms, diabetic, 342 ; 
gastro-intestinal, 259, 283, 288, 
342; hepatic, 277; nephritic, 433. 

Tracheal stenosis, effect of, on re- 
spiratory movements, 202. 

Tremor, 471. 

Tricuspid lesions, 42. 

Trigeminal nerve, relation of, to 
trophic disturbances in the eyes 
and face, 490. 

Tuberculosis, anaemia in, 134; heart 
hypertrophy in, 45. 

Tuberculosis of the lymphatic 
glands, relation of, to Hodgkin's 
disease, 155. 

Tumors, malignant, anaemia from, 
134, 138; proteid destruction 
from, 331. 

Tyrosin, relation of, to alkaptonu- 
ria, 345- 

Ulcer of the stomach, 244-247. 

Uraemia, 433 _ 436. 

Urea, formation of, 344. 

Urethral fever, 404. 

Uric acid, formation and excretion 
of, 368; in leukaemia, 370; in 
gout, 373; in calculi, 438. 

Uric acid infarcts of the new-born, 
370, 439- 

Uric acid stones, 438. 

Urinary bladder, relation of, to 
renal pelves, 436; calculi in, 438. 

Urinary passages, formation of cal- 
culi in, 438-441 ; inflammations of, 
437 ; painful sensations in, 441. 



Urine, characteristics of, in acido- 
sis, 337; in diabetes insipidus, 
416 ; in diabetes mellitus, 352 ; in 
fever, 400, 408, 427, 428; in hae- 
moglobinaemia, 149; in nephritic 
cedema, 119; in pernicious anae- 
mia, 140. 

Urine, secretion of, influence of 
composition of blood in, 429, 430; 
of circulation through kidneys, 
414, 417; of obstruction to escape 
of, 418; of lesions of the se- 
creting membrane, 419; results 
of disturbances of secretion of, 
432. 

Vaccination, 194. 

Vagina, infections in, 188. 

Vagus, relation of, to arrhythmia, 

93 ; to bradycardia, 83, 84 ; to 

respirations, 203 ; to tachycardia, 

78-79; vagus tonus in old age, 

77- 
Valvular disease. See Heart. 
Vascular disease, relation of, to 

muscular weakness, 454. 
Venous murmurs, 115. 
Venous pulse, 77. 
Vesical tenesmus, 441. 
Vocal cords, paralysis of, 204; 

spasmodic closure of, 202. 
Volume of blood expelled from the 

heart under varying conditions, 

25- 
Volvulus, 303. 
Vomiting, 260—261. 

Water, absorption of, through in- 
testines, 292; in blood serum in 
chlorosis, 131 ; elimination of, in 
fever, 386, 407 ; elimination of, 
through kidneys, 414, 415, 417, 
420; influence of, on fat metabo- 
lism, 324; amount of, in red 
blood-corpuscles, 141 ; retention 
of, in nephritis, 119, 120, 175, 176. 



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